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Melanoma: HELP
Articles by Agop Y. Bedikian
Based on 50 articles published since 2008
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Between 2008 and 2019, A. Bedikian wrote the following 50 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Does complete response to systemic therapy in patients with stage IV melanoma translate into long-term survival? 2011

Bedikian, Agop Y / Johnson, Marcella M / Warneke, Carla L / Papadopoulos, Nicholas E / Kim, Kevin B / Hwu, Wen-Jen / McIntyre, Susan / Rohlfs, Michelle / Homsi, Jade / Hwu, Patrick. ·Departments of aMelanoma Medical Oncology bBioinformatics cNursing, MD, Anderson Cancer Center, University of Texas, Houston, Texas, USA. ·Melanoma Res · Pubmed #21102360.

ABSTRACT: The aim of this study was to determine the impact of complete response (CR) to systemic therapy on survival. We reviewed the cases of 647 chemo-naive patients with metastatic melanoma who were treated with cisplatin-vinblastine-dacarbazine or cisplatin-taxol-dacarbazine alone, or cisplatin-vinblastine-dacarbazine together with interferon α or interleukin-2 plus interferon α. After excluding patients with uveal melanoma and patients who had resection of metastases, 567 patients were eligible to participate in this analysis. An event chart is presented for the 51 patients with CR and for three random samples of patients without CR. We compared overall survival of responders versus nonresponders using response as a time-dependent covariate in a Cox proportional hazards model. In addition, we used the landmark method, choosing 6 months as the landmark. Logistic regression techniques were used to determine factors associated with CR to therapy. All P values were 2-tailed and considered significant at α less than 0.05. Analyses were conducted using SAS for Windows. In this analysis, CR was associated with patients who were younger, male, and who had better performance status, lower M-stage, no liver metastases, and no visceral sites involved, normal LDH and had received biochemotherapy. While accounting for these factors, the relationship between CR and survival remained statistically significant, suggesting a causal relationship between response and survival. Using 6-month landmark analysis method, we still find a significant difference in overall survival between response groups, favoring patients who achieved CR with systemic therapy. In conclusion, CR to systemic therapy is associated with long-term survival in patients with stage IV melanoma.

2 Review Allovectin-7 therapy in metastatic melanoma. 2008

Bedikian, Agop Y / Del Vecchio, Michele. ·The University of Texas MD Anderson Cancer Center, Department of Melanoma Medical Oncology, 1515 Holcombe Blvd, Box 430, Houston, TX 77030, USA. abedikia@mdanderson.org ·Expert Opin Biol Ther · Pubmed #18476795.

ABSTRACT: BACKGROUND: Patients with metastatic melanoma are immunosuppressed by the growing tumor. Allovectin-7 therapy is a form of active immunotherapy that aims at immunization of the host with substances designed to elicit an immune reaction that will eliminate or slow down the growth and spread of the cancer. OBJECTIVE: to describe the rationale for immunotherapy with Allovectin-7 and assess its safety profile and efficacy based on the results of completed melanoma clinical trials. METHODS: we reviewed both the published medical literature and the results of trials pending publication. RESULTS/CONCLUSION: Allovectin-7 is a safe and active immunotherapeutic agent. It induces local and systemic durable responses in patients with metastatic melanoma.

3 Clinical Trial A phase II study of ipilimumab plus temozolomide in patients with metastatic melanoma. 2017

Patel, Sapna P / Kim, Dae Won / Bassett, Roland L / Cain, Suzanne / Washington, Edwina / Hwu, Wen-Jen / Kim, Kevin B / Papadopoulos, Nicholas E / Homsi, Jade / Hwu, Patrick / Bedikian, Agop Y. ·Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. sppatel@mdanderson.org. · Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. · Moffitt Cancer Center, 12902 USF Magnolia Dr., Tampa, FL, 33612, USA. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. · California Pacific Medical Center, 2323 Sacramento St. #2, San Francisco, CA, 94115, USA. · The University of Texas Banner MD Anderson Cancer Center, 2946 E Banner Gateway Dr., Gilbert, AZ, 85234, USA. ·Cancer Immunol Immunother · Pubmed #28612140.

ABSTRACT: Checkpoint blockade has revolutionized the treatment of melanoma; however, it benefits only the minority of patients. Several agents have been combined with immunotherapy to improve T-cell activation and persistence including growth factor, chemotherapy, and radiation. Preclinical data suggest that temozolomide, which metabolizes to the same active compound as dacarbazine, selectively depletes regulatory T cells. This potential immunomodulatory effect of temozolomide provides rationale for combination with ipilimumab. We performed an open-label single-arm phase II study of ipilimumab plus temozolomide in the frontline setting for patients with metastatic melanoma and LDH ≤2× upper limit of normal. Ipilimumab was given at 10 mg/kg on day 1 and temozolomide 200 mg/m

4 Clinical Trial A phase I study of TPI 287 in combination with temozolomide for patients with metastatic melanoma. 2016

McQuade, Jennifer L / Posada, Liberty P / Lecagoonporn, Srisuda / Cain, Suzanne / Bassett, Roland L / Patel, Sapna P / Hwu, Wen-Jen / Hwu, Patrick / Davies, Michael A / Bedikian, Agop Y / Amaria, Rodabe N. ·Departments of aMelanoma Medical Oncology bBiostatistics cSystems Biology, UT MD Anderson Cancer Center, Houston, Texas, USA. ·Melanoma Res · Pubmed #27540836.

ABSTRACT: TPI 287 is a synthetic taxane derivative with structural modifications allowing for central nervous system penetration and potential circumvention of multidrug resistance efflux pump mechanisms. The aim of this phase I study was to determine the maximum tolerated dose of the combination of TPI 287 and temozolomide in metastatic melanoma. Patients with stage IV unresectable or recurrent stage III melanoma were eligible. Stable untreated or treated brain metastases were allowed. Patients with previous taxane exposure were excluded. TPI 287 was administered intravenously on days 1, 8, and 15 and temozolomide was taken orally daily on days 1-5 of a 28-day cycle. Responses were assessed every two cycles according to WHO criteria. A total of 21 patients were enrolled. The maximum tolerated dose of the combination at this schedule was determined to be 125 mg/m intravenous of TPI 287 and 110 mg/m of oral temozolomide. The dose-limiting toxicity was neuropathy and six patients experienced grade III neuropathy. All patients were evaluable for tumor response. There were no complete responses; there were two partial responses and seven patients had stable disease (overall response rate 9.5% and disease control rate 42.9%). Three patients had stable disease in the brain despite progressive extracranial disease. The combination of TPI 287 and temozolomide is well tolerated in patients with metastatic melanoma, with the exception of neuropathy. The central nervous system penetration of both agents makes this a rational combination for further testing in primary and metastatic brain lesions.

5 Clinical Trial A phase 2 randomised study of ramucirumab (IMC-1121B) with or without dacarbazine in patients with metastatic melanoma. 2014

Carvajal, Richard D / Wong, Michael K / Thompson, John A / Gordon, Michael S / Lewis, Karl D / Pavlick, Anna C / Wolchok, Jedd D / Rojas, Patrick B / Schwartz, Jonathan D / Bedikian, Agop Y. ·Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Electronic address: carvajar@mskcc.org. · USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA. · Seattle Cancer Care Alliance, Seattle, WA, USA. · Pinnacle Oncology Hematology, Scottsdale, AZ, USA. · University of Colorado Denver, Aurora, CO, USA. · New York University, New York, NY, USA. · Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · ImClone Systems LLC, a wholly-owned subsidiary of Eli Lilly and Company, Bridgewater, NJ, USA. · MD Anderson Cancer Center, Houston, TX, USA. ·Eur J Cancer · Pubmed #24930625.

ABSTRACT: BACKGROUND: To evaluate the efficacy and safety of ramucirumab (IMC-1121B; LY3009806), a fully human monoclonal antibody targeting the vascular endothelial growth factor receptor-2, alone and in combination with dacarbazine in chemotherapy-naïve patients with metastatic melanoma (MM). METHODS: Eligible patients received ramucirumab (10mg/kg) + dacarbazine (1000 mg/m(2)) (Arm A) or ramucirumab only (10mg/kg) (Arm B) every 3 weeks. The primary end-point was progression-free survival (PFS); secondary end-points included overall survival (OS), overall response and safety. FINDINGS: Of 106 randomised patients, 102 received study treatment (Arm A, N=52; Arm B, N=50). Baseline characteristics were similar in both arms. Median PFS was 2.6 months (Arm A) and 1.7 months (Arm B); median 6-month PFS rates were 30.7% and 17.9% and 12-month PFS rates were 23.7% and 15.6%, respectively. In Arm A, 9 (17.3%) patients had partial response (PR) and 19 (36.5%), stable disease (SD); PR and SD in Arm B were 2 (4.0%) and 21 (42.0%), respectively. Median OS was 8.7 months in Arm A and 11.1 months in Arm B. Patients in both arms tolerated the treatment with limited Grade 3/4 toxicities. INTERPRETATION: Ramucirumab alone or in combination with dacarbazine was associated with an acceptable safety profile in patients with MM. Although the study was not powered for comparison between treatment arms, PFS appeared greater with combination therapy. Sustained disease control was observed on both study arm.

6 Clinical Trial Phase I trial of biochemotherapy with cisplatin, temozolomide, and dose escalation of nab-paclitaxel combined with interleukin-2 and interferon-α in patients with metastatic melanoma. 2014

Alrwas, Anas / Papadopoulos, Nicholas E / Cain, Suzanne / Patel, Sapna P / Kim, Kevin B / Deburr, Tawania L / Bassett, Roland / Hwu, Wen-Jen / Bedikian, Agop Y / Davies, Michael A / Woodman, Scott E / Hwu, Patrick. ·aHealth Science Center, University of Oklahoma, Oklahoma City, Oklahoma Departments of bMelanoma Medical Oncology cPalliative Care and Rehabilitative Medicine dBiostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. ·Melanoma Res · Pubmed #24743052.

ABSTRACT: The primary objective of this study was to determine the safety, toxicity, and maximum tolerated dose of nanoparticle albumin-bound (nab)-paclitaxel as part of biochemotherapy for metastatic melanoma and to determine whether substituting nab-paclitaxel for less potent agents could increase response rates and duration. Treatment consisted of intravenous cisplatin (20 mg/m) on days 1-4, oral temozolomide (250 mg/m) on days 1-3, subcutaneous interferon-α (5×10 IU/m) on days 1-5, and continuous intravenous interleukin-2 (9×10 IU/m) for 96 h on days 1-4. A standard 3+3 dose escalation method was used; the nab-paclitaxel starting dose was 100 mg/m on day 1 and 70 mg/m on day 5. The treatment cycle was repeated every 3 weeks and toxicity was assessed weekly. Ten patients were enrolled. Dose-limiting toxicities included diarrhea, transaminasemia, and neutropenia. The maximum tolerated dose was not identified because the nab-paclitaxel dose on day 1 at the lowest planned dose (80 mg/m) caused dose-limiting toxicity in two of five patients. Of the nine patients who were evaluable for response, five had a partial response. The median time to disease progression was 5.30 months and the median overall survival was 8.73 months. Six patients developed central nervous system metastasis at a median of 5.33 months after treatment initiation. Biochemotherapy including nab-paclitaxel according to the doses and schedule regimen used in the present study has significant toxicity. Substituting dacarbazine with temozolomide did not prevent central nervous system metastasis in patients with metastatic melanoma.

7 Clinical Trial Dacarbazine with or without oblimersen (a Bcl-2 antisense oligonucleotide) in chemotherapy-naive patients with advanced melanoma and low-normal serum lactate dehydrogenase: 'The AGENDA trial'. 2014

Bedikian, Agop Y / Garbe, Claus / Conry, Robert / Lebbe, Celeste / Grob, Jean J / Anonymous1690789. ·aDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas bDivision of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, Alabama, USA cDermatology Polyclinic, Saint Louis Hospital, Paris dDepartment of Dermatology, Aix-Marseille University, Marseille, France eDepartment of Dermatology, University Medical Centre, Tubingen, Germany. ·Melanoma Res · Pubmed #24667300.

ABSTRACT: In a previous large randomized, open-label study, retrospective subset analysis revealed that the addition of the Bcl-2 antisense oligonucleotide oblimersen to dacarbazine (Dac) significantly improved overall survival, progression-free survival, and the response rate in chemotherapy-naive patients with advanced melanoma and normal baseline serum lactate dehydrogenase (LDH) levels. To confirm and expand on this observation, we conducted a prospective double-blind, placebo-controlled study to determine whether oblimersen augmented the efficacy of Dac in advanced melanoma patients with low-normal baseline LDH levels. A total of 314 chemotherapy-naive patients were randomly assigned to receive Dac (1000 mg/m(2)) preceded by a 5-day continuous intravenous infusion of either oblimersen sodium (7 mg/kg/day) or placebo every 21 days for less than eight cycles. Co-primary efficacy endpoints were overall survival and progression-free survival. Response and progression of the disease were assessed by independent blinded review of computed tomography scan images. No difference in overall nor progression-free survival was observed between the Dac-oblimersen and Dac-placebo groups. Although the overall (17.2 vs. 12.1%) and durable (10.8 vs. 7.6%) response rates numerically favored Dac-oblimersen over Dac-placebo, they did not differ significantly (P=0.19 and 0.32, respectively). The incidence of hematologic adverse events, particularly thrombocytopenia and neutropenia, was higher in the Dac-oblimersen group than in the Dac-placebo group. Withdrawals from the study because of treatment-related adverse events were low (i.e. <2.5%) in both groups. The addition of oblimersen to Dac did not significantly improve overall survival nor progression-free survival in patients with advanced melanoma and low-normal levels of LDH at baseline.

8 Clinical Trial Chemical castration of melanoma patients does not increase the frequency of tumor-specific CD4 and CD8 T cells after peptide vaccination. 2013

Vence, Luis M / Wang, Chiyu / Pappu, Himabindu / Anson, Ryan E / Patel, Tejal A / Miller, Priscilla / Bassett, Roland / Lizee, Gregory / Overwijk, Willem W / Komanduri, Krishna / Benjamin, Cara / Alvarado, Gladys / Patel, Sapna P / Kim, Kevin / Papadopoulos, Nicholas E / Bedikian, Agop Y / Homsi, Jade / Hwu, Wen-Jen / Boyd, Richard / Radvanyi, Laszlo / Hwu, Patrick. ·M.D. Anderson Cancer Center, University of Texas, Houston, TX 77054, USA. lmvence@mdanderson.org ·J Immunother · Pubmed #23603862.

ABSTRACT: Peptide vaccination against tumor-associated antigens remains one of the most common methods of immunization in cancer vaccine clinical trials. Although peptide vaccination has been reported to increase circulating antigen-specific T-cells, they have had limited clinical efficacy and there is a necessity to increase their capacity to generate strong antitumor responses. We sought to improve the clinical efficacy of peptide-based vaccines in cancer immunotherapy of metastatic melanoma using a LHRH agonist (leuprolide) as adjuvant. Seventy HLA-A*0201 stage IIb-IV melanoma patients were vaccinated with class I HLA-A*0201-restricted gp100209-2M peptide and stratified for HLA-DP4 restriction. HLA-DP4 patients were also vaccinated with class II HLA-DP4-restricted MAGE-3243-258 peptide. Patients from both groups were randomized to receive 2 doses of leuprolide or not. Here we report the increase in PBMC TREC levels at week 24 after peptide vaccination, which was independent of the leuprolide treatment. This change was mirrored by a small increase in the TREC-enriched CD8CD45RAROCD27CD103, but not the TREC-enriched CD4CD45RAROCD31 T-cell population. Serum concentration of 2 important factors for thymopoiesis was measured: insulin growth factor 1 (IGF-1) levels were not changed, whereas a moderate increase in IL-7 levels was noted in the sera of all patients 6 weeks after vaccination. Increased expression of CD127 (IL-7 receptor-α) at week 24, compared with baseline, was only seen in the CD8CD45RAROCD27CD103 T-cell population. Our results suggest that leuprolide has no effect on thymic output when used as peptide vaccine adjuvant, but IFA-based peptide vaccination may unexpectedly affect the thymus by increasing thymic output of new T cells.

9 Clinical Trial Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. 2012

Radvanyi, Laszlo G / Bernatchez, Chantale / Zhang, Minying / Fox, Patricia S / Miller, Priscilla / Chacon, Jessica / Wu, Richard / Lizee, Gregory / Mahoney, Sandy / Alvarado, Gladys / Glass, Michelle / Johnson, Valen E / McMannis, John D / Shpall, Elizabeth / Prieto, Victor / Papadopoulos, Nicholas / Kim, Kevin / Homsi, Jade / Bedikian, Agop / Hwu, Wen-Jen / Patel, Sapna / Ross, Merrick I / Lee, Jeffrey E / Gershenwald, Jeffrey E / Lucci, Anthony / Royal, Richard / Cormier, Janice N / Davies, Michael A / Mansaray, Rahmatu / Fulbright, Orenthial J / Toth, Christopher / Ramachandran, Renjith / Wardell, Seth / Gonzalez, Audrey / Hwu, Patrick. ·Departments of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. lradvanyi@mdanderson.org ·Clin Cancer Res · Pubmed #23032743.

ABSTRACT: PURPOSE: Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a promising treatment for metastatic melanoma unresponsive to conventional therapies. We report here on the results of an ongoing phase II clinical trial testing the efficacy of ACT using TIL in patients with metastatic melanoma and the association of specific patient clinical characteristics and the phenotypic attributes of the infused TIL with clinical response. EXPERIMENTAL DESIGN: Altogether, 31 transiently lymphodepleted patients were treated with their expanded TIL, followed by two cycles of high-dose interleukin (IL)-2 therapy. The effects of patient clinical features and the phenotypes of the T cells infused on the clinical response were determined. RESULTS: Overall, 15 of 31 (48.4%) patients had an objective clinical response using immune-related response criteria (irRC) with 2 patients (6.5%) having a complete response. Progression-free survival of more than 12 months was observed for 9 of 15 (60%) of the responding patients. Factors significantly associated with the objective tumor regression included a higher number of TIL infused, a higher proportion of CD8(+) T cells in the infusion product, a more differentiated effector phenotype of the CD8(+) population, and a higher frequency of CD8(+) T cells coexpressing the negative costimulation molecule "B- and T-lymphocyte attenuator" (BTLA). No significant difference in the telomere lengths of TIL between responders and nonresponders was identified. CONCLUSION: These results indicate that the immunotherapy with expanded autologous TIL is capable of achieving durable clinical responses in patients with metastatic melanoma and that CD8(+) T cells in the infused TIL, particularly differentiated effectors cells and cells expressing BTLA, are associated with tumor regression.

10 Clinical Trial BRAF, NRAS and KIT sequencing analysis of spindle cell melanoma. 2012

Kim, Jinhyun / Lazar, Alexander J / Davies, Michael A / Homsi, Jade / Papadopoulos, Nicholas E / Hwu, Wen-Jen / Bedikian, Agop Y / Woodman, Scott E / Patel, Sapna P / Hwu, Patrick / Kim, Kevin B. ·Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. ·J Cutan Pathol · Pubmed #22809251.

ABSTRACT: BACKGROUND: Spindle cell melanoma represents a rare but distinct subset of melanoma, and its genomic spectrum has not been fully defined. METHODS: We searched our institutional database for patients with a diagnosis of pure spindle cell-type melanoma whose tumors had been analyzed for BRAF, NRAS, and KIT mutations using pyrosequencing technique. RESULTS: We identified 24 patients with spindle cell melanoma, including 10 patients with desmoplastic melanoma, whose tumors had been analyzed for at least one of the three genes. The median Breslow thickness was 2.6 mm, and the most common site of the primary melanoma was the trunk, followed by the head and neck region. BRAF, NRAS and KIT genomic sequencing was performed successfully in 20, 18 and 14 patients, respectively. Among the 20 melanomas with completed BRAF-sequencing analysis, 6 (30%) harbored a mutation, of which 5 (83%) had a V600E mutation and 1 (17%) had a V600R mutation. None of the melanomas harbored NRAS or KIT mutations. CONCLUSION: As has been reported in other common types of melanoma, V600 BRAF mutation is the most common mutation of those tested in spindle cell melanoma. NRAS or KIT mutation appears to be rare, if not completely absent.

11 Clinical Trial A randomized phase II study of cilengitide (EMD 121974) in patients with metastatic melanoma. 2012

Kim, Kevin B / Prieto, Victor / Joseph, Richard W / Diwan, Abdul H / Gallick, Gary E / Papadopoulos, Nicholas E / Bedikian, Agop Y / Camacho, Luis H / Hwu, Patrick / Ng, Chaan S / Wei, Wei / Johnson, Marcella M / Wittemer, Sabine M / Vardeleon, Anna / Reckeweg, Aaron / Colevas, A Dimitrios. ·Department of Melanoma Medical Oncology, MD Anderson Cancer Center, The University of Texas, Houston, Texas 77030, USA. kkim@mdanderson.org ·Melanoma Res · Pubmed #22668797.

ABSTRACT: Cilengitide (EMD 121974) is a selective inhibitor of integrins αvβ3 and αvβ5. The αvβ3 promotes the proliferation of tumor-associated endothelial cells and potentially the survival of melanoma cells. We conducted a randomized phase II trial in patients with metastatic melanoma to evaluate the clinical efficacy of cilengitide. Patients with stage IV or unresectable stage III melanoma who were either chemonaive or who had previously received one systemic therapy were enrolled. Patients were randomly assigned to either 500 or 2000 mg of cilengitide administered intravenously twice weekly. The primary aim of this study was to determine the progression-free survival rate at 8 weeks. Tumor samples and blood samples were collected for pharmacodynamic and pharmacokinetic studies. Twenty-nine patients were enrolled, of whom 26 were treated (14 at 500 mg and 12 at 2000 mg). Among those treated, only three were progression free at 8 weeks: two in the 500 mg arm and one in the 2000 mg arm. One patient in the 2000 mg arm showed a prolonged partial response after an initial 28% enlargement of her target lesions. The treatment was well tolerated without clinically significant adverse events. The sole responder and one of two patients with stable disease had no αvβ3 expression at baseline. Overall, αvβ3 expression was decreased by day 8 of the treatment (P=0.05). Cilengitide was well tolerated by patients in both the treatment arms but had minimal clinical efficacy as a single-agent therapy for metastatic melanoma, and the efficacy was not related to baseline αvβ3 expression.

12 Clinical Trial Comparison of two dosing schedules of palonosetron for the prevention of nausea and vomiting due to interleukin-2-based biochemotherapy. 2012

Noor, Rahat / Bedikian, Agop Y / Mahoney, Sandy / Bassett, Roland / Kim, Kevin / Papadopoulos, Nicholas / Hwu, Wen-Jen / Hwu, Patrick / Homsi, Jade. ·Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. ·Support Care Cancer · Pubmed #22274951.

ABSTRACT: BACKGROUND: Treatment of metastatic melanoma with interleukin-2-based biochemotherapy involves administration of a combination of moderately and highly emetogenic chemotherapies over 5 days. Corticosteroids for the prevention of biochemotherapy-induced nausea and vomiting (CINV) are contraindicated because they cause lysis of LAK cells produced in response to interleukin-2. Palonosetron is a long-acting, highly potent, second-generation serotonin receptor antagonist. The recommended dosing schedule of palonosetron for the control of CINV due to biochemotherapy is not known. METHODS: In a phase II design, treatment-naïve patients with metastatic melanoma undergoing the first cycle of biochemotherapy were randomized to receive palonosetron 0.25 mg intravenously for CINV prophylaxis on either days 1 and 4 (schedule 1) or days 1, 3, and 5 (schedule 2). All patients received dacarbazine on day 1, cisplatin, vinblastine, and interleukin-2 on days 1-4, and interferon alpha-2b on days 1-5. We evaluated and compared, by palonosetron dosing schedule, the pattern and the severity of CINV during the first 7 days of treatment and the duration of the 21-day cycle as well as the impact on daily function with the Functional Living Index-Emesis. RESULTS: Thirty patients (median age 53 years) were enrolled. Eighteen (60%) were men. A consistent trend of a better control of both nausea and vomiting favoring schedule 2 was observed during the first 7 days and throughout the cycle. Significantly more patients experienced nausea on any day during the first 7 days on schedule 1 (mean number of episodes 8.1 ± 1.5) than on schedule 2 (mean number of episodes 5.6 ± 2.3, p = 0.028). The impact on daily function was similar between the two groups. CONCLUSIONS: Both dosing schedules of palonosetron were tolerated well. Alternate day dosing of palonosetron was more effective in controlling CINV in this patient population.

13 Clinical Trial Phase I study of the combination of sorafenib and temsirolimus in patients with metastatic melanoma. 2012

Davies, Michael A / Fox, Patricia S / Papadopoulos, Nicholas E / Bedikian, Agop Y / Hwu, Wen-Jen / Lazar, Alexander J / Prieto, Victor G / Culotta, Kirk S / Madden, Timothy L / Xu, Quanyun / Huang, Sha / Deng, Wanleng / Ng, Chaan S / Gupta, Sanjay / Liu, Wenbin / Dancey, Janet E / Wright, John J / Bassett, Roland L / Hwu, Patrick / Kim, Kevin B. ·Departments of Melanoma Medical Oncology, Systems Biology, Biostatistics, Pathology, Experimental Therapeutics, and Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. ·Clin Cancer Res · Pubmed #22223528.

ABSTRACT: PURPOSE: This phase I clinical trial was conducted to determine the safety, efficacy, and molecular effects of sorafenib with temsirolimus in patients with advanced melanoma. PATIENTS AND METHODS: Patients with stage IV or unresectable or recurrent stage III melanoma and Eastern Cooperative Oncology Group performance status of 0 to 1 were eligible. Sorafenib was given orally once or twice daily and temsirolimus was given i.v. weekly, both starting on day 1, with a 4-week cycle. Responses were assessed every 2 cycles per Response Evaluation Criteria in Solid Tumors criteria. Consenting patients with accessible tumors underwent optional tumor biopsies before treatment and after the second infusion of temsirolimus. Tumor biopsies were analyzed for activating mutations in BRAF and NRAS, and for expression of P-extracellular signal-regulated kinase (P-ERK) and P-S6 proteins. RESULTS: A total of 25 patients were accrued to the study. The maximum tolerated doses were sorafenib 400 mg every morning and 200 mg every evening and temsirolimus 25 mg i.v. weekly. Dose-limiting toxicities included thrombocytopenia, hand-foot syndrome, serum transaminase elevation, and hypertriglyceridemia. There were no complete or partial responses with the combination; 10 patients achieved stabilization of disease as their best response. The median progression-free survival was 2.1 months. Matching pretreatment and day 15 tumor biopsies showed marked inhibition of P-S6 with treatment in 3 of 4 evaluable patients, but minimal inhibition of P-ERK. CONCLUSIONS: Combination therapy with sorafenib and temsirolimus resulted in significant toxicity at higher dose levels, failed to achieve any clinical responses in genetically unselected patient population, and did not inhibit P-ERK.

14 Clinical Trial A phase II study of gefitinib in patients with metastatic melanoma. 2011

Patel, Sapna P / Kim, Kevin B / Papadopoulos, Nicholas E / Hwu, Wen-Jen / Hwu, Patrick / Prieto, Victor G / Bar-Eli, Menashe / Zigler, Maya / Dobroff, Andrey / Bronstein, Yulia / Bassett, Roland L / Vardeleon, Anna G / Bedikian, Agop Y. ·Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. ·Melanoma Res · Pubmed #21738104.

ABSTRACT: Gefitinib is an inhibitor of the epidermal growth factor receptor, which is frequently expressed on both choroidal and nonchoroidal melanoma cells. We evaluated the clinical efficacy of gefitinib in patients with metastatic melanoma. Patients with stage IV or unresectable stage III melanoma and Zubrod performance status of less than or equal to 2 were eligible. Previous systemic treatment for metastatic disease was required. The dose of oral gefitinib was 250 mg administered daily, and tumor response was evaluated every 6 weeks. Forty-six patients with nonchoroidal melanoma and six with choroidal melanoma were treated, and 48 were evaluable for response. The median age was 62.5 years. Forty-one patients (79%) had stage M1c disease. There were no drug-related grade 4 or 5 adverse events, and fatigue was the only grade 3 adverse event that occurred in more than 5% of patients. Two patients (4%) had partial responses and 13 patients (27%) had disease stabilization. The two responders had a median duration of response of 10.9 months. The median overall progression-free survival was 1.4 months and the median overall survival was 9.7 months. Among the patients with sufficient tissues obtained before and 6 weeks after starting gefitinib administration, there were no notable trends in the changes of the tumoral expression of p-ERK1/2, p-AKT, PAK1, and serum levels of vascular endothelial growth factor or IL-8 with treatment. We concluded that gefitinib was well tolerated but had minimal clinical efficacy as a single-agent therapy for unselected patients with metastatic melanoma.

15 Clinical Trial Impact of clinical and pathologic features on tumor-infiltrating lymphocyte expansion from surgically excised melanoma metastases for adoptive T-cell therapy. 2011

Joseph, Richard W / Peddareddigari, Vijay R / Liu, Ping / Miller, Priscilla W / Overwijk, Willem W / Bekele, Nebiyou B / Ross, Merrick I / Lee, Jeffrey E / Gershenwald, Jeffrey E / Lucci, Anthony / Prieto, Victor G / McMannis, John D / Papadopoulos, Nicholas / Kim, Kevin / Homsi, Jade / Bedikian, Agop / Hwu, Wen-Jen / Hwu, Patrick / Radvanyi, Laszlo G. ·Department of Melanoma Medical Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA. ·Clin Cancer Res · Pubmed #21632855.

ABSTRACT: PURPOSE: Clinical trials on adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) have shown response rates of over 50% in refractory melanoma. However, little is known how clinical and pathologic features impact TIL outgrowth isolated from metastatic melanoma tumors. EXPERIMENTAL DESIGN: We analyzed the impact of clinical and pathologic features on initial TIL outgrowth in 226 consecutive patients undergoing tumor resection. Successful initial TIL outgrowth was defined as ≥40 million viable lymphocytes harvested from all tumor fragments in a 5-week culture. To normalize for the different size of resected tumors and thus available tumor fragments, we divided the number of expanded TIL by the starting number of tumor fragments (TIL/fragment). RESULTS: Overall, initial TIL outgrowth was successful in 62% of patients, with patients ≤30 years of age (94%; P = 0.01) and female patients (71% vs. 57% for males; P = 0.04) having the highest rate of success. Systemic therapy 30 days before tumor harvest negatively impacted initial TIL outgrowth compared to patients who never received systemic therapy (47% vs. 71%, P = 0.02). Biochemotherapy within 0 to 60 days of tumor harvest negatively impacted the initial TIL outgrowth with a success rate of only 16% (P < 0.0001). CONCLUSION: Parameters such as age, sex, and the type and timing of prior systemic therapy significantly affect the success rate of the initial TIL outgrowth from tumor fragments for ACT; these parameters may be helpful in selecting patients for melanoma ACT.

16 Clinical Trial Pharmacokinetics and safety of Marqibo (vincristine sulfate liposomes injection) in cancer patients with impaired liver function. 2011

Bedikian, Agop Y / Silverman, Jeffrey A / Papadopoulos, Nicholas E / Kim, Kevin B / Hagey, Anne E / Vardeleon, Anna / Hwu, Wen-Jen / Homsi, Jade / Davies, Michael / Hwu, Patrick. ·Department of Melanoma Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA. ·J Clin Pharmacol · Pubmed #20978276.

ABSTRACT: Marqibo (vincristine sulfate liposome injection, VSLI) is a novel liposomal formulation of vincristine sulfate (VCR) being developed for the systemic treatment of cancer. This study evaluated the pharmacokinetics (PK) of Marqibo in subjects with melanoma and impaired hepatic function. Calculated PK parameters were similar in subjects with impaired liver function compared with those in subjects with adequate liver function. Subjects with impaired liver function universally had a monoexponential total plasma VCR concentration versus time decline, whereas two thirds of subjects with adequate liver function had a biexponential decline profile. Because one third of subjects with normal hepatic function demonstrated monoexponential disposition, lack of biexponential disposition in the hepatically impaired subjects cannot be clearly attributed to liver impairment. VSLI was generally well tolerated in all subjects.

17 Clinical Trial Phase 3 study of docosahexaenoic acid-paclitaxel versus dacarbazine in patients with metastatic malignant melanoma. 2011

Bedikian, A Y / DeConti, R C / Conry, R / Agarwala, S / Papadopoulos, N / Kim, K B / Ernstoff, M. ·Department of Melanoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. abedikia@mdanderson.org ·Ann Oncol · Pubmed #20855467.

ABSTRACT: BACKGROUND: Docosahexaenoic acid-paclitaxel (DHA-paclitaxel, Taxoprexin(®)) is made by covalently conjugating the essential fatty acid DHA to the paclitaxel molecule. Preclinical studies of DHA-paclitaxel have demonstrated increased activity relative to paclitaxel and the potential for an improved therapeutic ratio. In the present study, the efficacy and toxicity profiles of DHA-paclitaxel were compared with those of dacarbazine. METHODS: In this study, 393 chemonaive patients with metastatic melanoma were randomly assigned to receive either DHA-paclitaxel at a starting dose of 900 mg/m(2) IV on day 1 every 3 weeks or dacarbazine at a starting dose of 1000 mg/m(2) IV on day 1 every 3 weeks. The primary end point of the study was the comparison of overall survival (OS). RESULTS: No significant difference in OS was noted between patients in the DHA-paclitaxel and dacarbazine arms. Similarly, there were no significant differences in response rate, duration of response, time to progression, and time to treatment failure between the two drugs. Safety results of the two drugs were as predicted from prior studies. Myelosuppression was more common with DHA-paclitaxel. CONCLUSIONS: DHA-paclitaxel was not superior to dacarbazine. We conclude that further studies with the drug on an every 3-week schedule in melanoma are not warranted.

18 Clinical Trial Phase 2 open-label study of weekly docosahexaenoic acid-paclitaxel in patients with metastatic uveal melanoma. 2010

Homsi, Jade / Bedikian, Agop Y / Papadopoulos, Nicholas E / Kim, Kevin B / Hwu, Wen-Jen / Mahoney, Sandy L / Hwu, Patrick. ·Department of Melanoma Medical Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA. jhomsi@mdanderson.org ·Melanoma Res · Pubmed #20881508.

ABSTRACT: Docosahexaenoic acid (DHA)-paclitaxel is a taxane with a unique pharmacokinetic profile. We investigated the safety and response rate of DHA-paclitaxel weekly in patients with metastatic uveal melanoma. Chemotherapy-naive and previously treated patients were eligible for this open-label phase II study. DHA-paclitaxel (500 mg/m²/week) was administered by a 1-hour intravenous infusion for five consecutive weeks in a 6-weeks cycle. Response was assessed using the Response Evaluation Criteria in Solid Tumors every 6 weeks. Twenty-two patients were enrolled. The patients' median age was 56 years (range: 33-79 years). Nine patients had a systemic therapy for metastatic disease earlier. The median number of treatment cycles was 1 (range 1-7 cycles). One chemonaive patient with liver metastases had partial response lasting for 5 months. Seven patients (32%) had stable disease with a median duration of 3 months (range: 3-7 months). The median overall survival was 9.8 months. Neutropenia (23%) and musculoskeletal pain (10%) were the most common grade 3 and grade 4 toxicities. As a single-agent therapy, DHA-paclitaxel is safe and well-tolerated in metastatic uveal melanoma patients. Its efficacy in this disease is limited with 32% of patients achieving stable disease. Further evaluation of DHA-paclitaxel in combination with other chemotherapeutic agents and/or targeted agents may improve its antitumor activity.

19 Clinical Trial Phase I safety study of lenalidomide and dacarbazine in patients with metastatic melanoma previously untreated with systemic chemotherapy. 2010

Hwu, Wen-Jen / Knight, Robert D / Patnana, Madhavi / Bassett, Roland / Papadopoulos, Nicholas E / Kim, Kevin B / Hwu, Patrick / Bedikian, Agop. ·Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030-4009, USA. wenjhwu@mdanderson.org ·Melanoma Res · Pubmed #20859231.

ABSTRACT: This phase I trial assessed the maximal tolerated dose (MTD) of dacarbazine in combination with lenalidomide in metastatic melanoma. Cohorts of three to six patients with metastatic melanoma without brain metastases were enrolled at each of three dose levels of dacarbazine: 600 mg/m², 800 mg/m², and 1000 mg/m² administered intravenously every 3 weeks. Lenalidomide (25 mg/day) was administered orally for 14 days followed by a 7-day rest. Safety was assessed every 3 weeks, and tumor response was evaluated every 6 weeks. An additional 10 patients were enrolled in an expansion cohort at MTD level. Twenty-eight chemotherapy-naive patients were enrolled. The MTD was determined to be dose level 2 (800 mg/m²). Three patients experienced a grade 4 adverse reaction; two pulmonary emboli and one cerebral ischemia. Two patients had a deep venous thrombosis. Of 27 patients assessable for disease response, two experienced a complete response and four experienced a partial response. The median overall survival was 10.6 months (range 1.6-46.0+ months). One patient had a small brain lesion at the baseline; 10 additional patients developed brain metastasis at 0-10.8 months after completion of study therapy. The combination of dacarbazine and lenalidomide is safe and well tolerated in patients with metastatic melanoma. Clinical activity was seen at the MTD level. Additional measures to prevent brain metastasis are needed for patients who achieve a response.

20 Clinical Trial A phase 2 study of high-dose Allovectin-7 in patients with advanced metastatic melanoma. 2010

Bedikian, Agop Y / Richards, Jon / Kharkevitch, Dmitri / Atkins, Michael B / Whitman, Eric / Gonzalez, Rene. ·Department of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, Texas, USA. ·Melanoma Res · Pubmed #20354459.

ABSTRACT: Allovectin-7, a bicistronic plasmid encoding human leukocyte antigen-B7 and beta-2 microglobulin formulated with a cationic lipid system, is an immunotherapeutic agent designed to express allogeneic major histocompatibility complex class I antigen upon intralesional administration. A phase 2 dose-escalation study (VCL-1005-208) was conducted to evaluate the safety and efficacy of Allovectin-7 in patients with metastatic melanoma. Eligible patients had stage III or IV metastatic melanoma recurrent or unresponsive to prior therapy, an Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients with brain or visceral (except lung) metastases, abnormal lactate dehydrogenase, or any lesion greater than 100 cm were excluded. Patients received six weekly intralesional injections followed by 3 weeks of observation and evaluation. Overall response was assessed using Response Evaluation Criteria in Solid Tumors guidelines. Patients with stable or responding disease were eligible to receive additional cycles of Allovectin-7. All 133 patients were evaluated for safety and 127 patients (2 mg, high dose) were evaluated for efficacy. Fifteen patients (11.8%, 95% confidence interval: 6.2-17.4) achieved an objective response with median duration of response of 13.8 months (95% confidence interval: 8.5, not estimable). A histological examination of tissue from two responding patients who had their lesions resected has shown no evidence of melanoma. Median time-to-progression in this study was 1.6 months. In conclusion, these results indicate that high-dose Allovectin-7 seems to be an active, well-tolerated treatment for selected stage III/IV metastatic melanoma patients with injectable cutaneous, subcutaneous, or nodal lesions.

21 Clinical Trial Phase I clinical trial of hepatic arterial infusion of cisplatin in combination with intravenous liposomal doxorubicin in patients with advanced cancer and dominant liver involvement. 2010

Tsimberidou, Apostolia M / Moulder, Stacy / Fu, Siqing / Wen, Sijin / Naing, Aung / Bedikian, Agop Y / Daring, Shawn / Uehara, Cynthia / Ng, Chaan / Wallace, Michael / Camacho, Luis / Kurzrock, Razelle. ·Phase I Program, Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. atsimber@mdanderson.org ·Cancer Chemother Pharmacol · Pubmed #20204368.

ABSTRACT: PURPOSE: We conducted a phase I study of hepatic arterial infusion (HAI) cisplatin and systemic chemotherapy in patients with advanced cancer and dominant liver involvement. METHODS: Patients were treated with HAI cisplatin 100-125 mg/m(2) (and 3,000 IU heparin) intraarterially and liposomal doxorubicin (doxil) 20-35 mg/m(2) IV (day 1) every 28 days. A "3 + 3" study design was used. RESULTS: Thirty patients were treated (median age, 56 years). Diagnoses were breast cancer (n = 11), colorectal cancer (n = 8), ocular melanoma (n = 4), and other (n = 7). The median number of prior therapies was 5. The maximum tolerated dose (MTD) was at the 100/35 mg/m(2) level. Dose-limiting toxicities were Grade 4 neutropenia (2 of 4 patients), and Grade 4 thrombocytopenia (n = 1) at the cisplatin 125 mg/m(2) and systemic doxil 35 mg/m(2) dose level. The most common toxicities were nausea/vomiting and fatigue. Of 24 patients evaluable for response, 4 (17%) had a partial response (PR) and 7 (29%) had stable disease (SD) for ≥4 months. Of the 11 patients with breast cancer, 3 (27%) had a PR and 5 (45%) had SD for ≥4 months. Of 4 patients with ocular melanoma, 1 had a PR and 1 SD for 4 months. One patient with hepatocellular carcinoma had SD for 4 months. Of 12 evaluable patients treated at the MTD, 2 (17%) had a PR and 5 (42%) had SD. CONCLUSION: The MTD was HAI cisplatin 100 mg/m(2) and systemic doxil 35 mg/m(2). This regimen demonstrated antitumor activity, especially in breast cancer.

22 Clinical Trial Autologous tumor-derived heat-shock protein peptide complex-96 (HSPPC-96) in patients with metastatic melanoma. 2010

Eton, Omar / Ross, Merrick I / East, Mary Jo / Mansfield, Paul F / Papadopoulos, Nicholas / Ellerhorst, Julie A / Bedikian, Agop Y / Lee, Jeffrey E. ·Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, USA. omar.eton@bmc.org ·J Transl Med · Pubmed #20109236.

ABSTRACT: BACKGROUND: Glycoprotein-96, a non-polymorphic heat-shock protein, associates with intracellular peptides. Autologous tumor-derived heat shock protein-peptide complex 96 (HSPPC-96) can elicit potent tumor-specific T cell responses and protective immunity in animal models. We sought to investigate the feasibility, safety, and antitumor activity of HSPPC-96 vaccines prepared from tumor specimens of patients with metastatic melanoma. METHODS: Patients with a Karnofsky Performance Status >70% and stage III or stage IV melanoma had to have a metastasis >3 cm in diameter resectable as part of routine clinical management. HSPPC-96 tumor-derived vaccines were prepared in one of three dose levels (2.5, 25, or 100 microg/dose) and administered as an intradermal injection weekly for 4 consecutive weeks. In vivo induction of immunity was evaluated using delayed-type hypersensitivity (DTH) to HSPPC-96, irradiated tumor, and dinitrochlorobenzene (DNCB). The gamma-interferon (IFNgamma) ELISPOT assay was used to measure induction of a peripheral blood mononuclear cell response against autologous tumor cells at baseline and at the beginning of weeks 3, 4, and 8. RESULTS: Among 36 patients enrolled, 72% had stage IV melanoma and 83% had received prior systemic therapy. The smallest tumor specimen from which HSPPC-96 was prepared weighed 2 g. Twelve patients (including 9 with stage IV and indicator lesions) had a negative DNCB skin test result at baseline. All 36 patients were treated and evaluable for toxicity and response. There were no serious toxicities. There were no observed DTH responses to HSPPC-96 or to autologous tumor cells before or during treatment. The IFNgamma-producing cell count rose modestly in 5 of 26 patients and returned to baseline by week 8, with no discernible association with HSPPC-96 dosing or clinical parameters. There were no objective responses among 16 patients with stage IV disease and indicator lesions. Among 20 patients treated in the adjuvant setting, 11 with stage IV melanoma at baseline had a progression-free and overall survival of 45% and 82%, respectively, with a median follow-up of 10 years. CONCLUSION: Treatment with autologous tumor-derived HSPPC-96 was feasible and safe at all doses tested. Observed immunological effects and antitumor activity were modest, precluding selection of a biologically active dose. Nevertheless, the 25-microg dose level was shown to be practical for further study.

23 Clinical Trial A randomized phase 2 study of etaracizumab, a monoclonal antibody against integrin alpha(v)beta(3), + or - dacarbazine in patients with stage IV metastatic melanoma. 2010

Hersey, Peter / Sosman, Jeffrey / O'Day, Steven / Richards, Jon / Bedikian, Agop / Gonzalez, Rene / Sharfman, William / Weber, Robert / Logan, Theodore / Buzoianu, Manuela / Hammershaimb, Luz / Kirkwood, John M / Anonymous2640649. ·Newcastle Melanoma Unit, Newcastle, Australia. ·Cancer · Pubmed #20108344.

ABSTRACT: BACKGROUND: The alpha (v) beta (3) (alpha(v)beta(3)) integrin is involved in intracellular signaling regulating cell proliferation, migration, and differentiation and is important for tumor-induced angiogenesis. METHODS: This phase 2, randomized, open-label, 2-arm study was designed to capture safety data and evaluate the antitumor efficacy of etaracizumab (Abegrin), an IgG1 humanized monoclonal antibody against the alpha(v)beta(3) integrin, in patients with previously untreated metastatic melanoma. The objective was to evaluate whether etaracizumab + or - dacarbazine had sufficient clinical activity to warrant further study in a phase 3 clinical trial. RESULTS: One hundred twelve patients were randomized to receive etaracizumab alone (N = 57) or etaracizumab + dacarbazine (N = 55). Safety of etaracizumab + or - dacarbazine was acceptable with infusion-related, gastrointestinal, and metabolic reactions being the most common adverse events (AEs). The majority of AEs were grade 1 or 2 in severity in both study arms; most events were not considered serious, except for cardiovascular (myocardial infarction, atrial fibrillation) and thromboembolic events, which occurred in 3 and 5 patients, respectively. None of the patients in the etaracizumab-alone study arm and 12.7% of patients in the etaracizumab + dacarbazine study arm achieved an objective response. The median duration of objective response in the etaracizumab + dacarbazine study arm was 4.2 months. Stable disease rate, time to progression (TTP), and progression-free survival (PFS) appeared to be similar between the 2 treatment arms. Stable disease occurred in 45.6% of patients in the etaracizumab-alone study arm and 40.0% of patients in the etaracizumab + dacarbazine study arm. Median TTP and median PFS were both 1.8 months in the etaracizumab-alone study arm and 2.5 and 2.6 months in the etaracizumab + dacarbazine study arm, respectively. Median overall survival was 12.6 months in the etaracizumab-alone study arm and 9.4 months in the etaracizumab + dacarbazine study arm. CONCLUSIONS: The survival results in both treatment arms of this study were considered unlikely to result in clinically meaningful improvement over dacarbazine alone.

24 Clinical Trial Results of a multicenter, randomized, double-blind, dose-evaluating phase 2/3 study of lenalidomide in the treatment of metastatic malignant melanoma. 2009

Glaspy, John / Atkins, Michael B / Richards, Jon M / Agarwala, Sanjiv S / O'Day, Steven / Knight, Robert D / Jungnelius, J Ulf / Bedikian, Agop Y. ·Department of Medicine, UCLA Medical Center, Los Angeles, CA 90095, USA. jglaspy@mednet.ucla.edu ·Cancer · Pubmed #19728370.

ABSTRACT: BACKGROUND: There are currently no systemic treatments for stage IV melanoma, which have been proven in randomized trials to benefit overall survival (OS). Lenalidomide has efficacy against melanoma in animal models and safety in phase 1 trials. The authors reported the results of a phase 2/3 study comparing the safety and efficacy of 2 doses of lenalidomide in patients with relapsed metastatic melanoma disease refractory to previous treatment with dacarbazine, temozolomide, interleukin-2, or interferon-alpha. METHODS: A total of 294 patients were randomized to oral lenalidomide at 5 mg or 25 mg dose. Tumor response, time to progression, and OS were evaluated. Treatment continued until disease progression or unacceptable adverse events. RESULTS: No significant differences in response rate, OS, or time to progression were observed between lenalidomide 25 mg versus 5 mg (overall response rate: 5.5% vs 3.4%, P = .38; median OS: 6.8 months vs 7.2 months, P = .71; and median time to progression: 2.2 months vs 1.9 months, P = .24). Myelosuppression was observed in 37.0% of patients in the 25 mg group and 13.7% of patients in the 5 mg group. Treatment-related serious adverse events were seen in 39.0% of patients at the 25 mg dose and 35.4% of patients at the 5 mg dose. CONCLUSIONS: Despite the occurrence of treatment-related serious adverse events, approximately 80% of patients continued treatment. The higher dose of lenalidomide did not improve response rate, time to progression, or OS of patients with relapsed/refractory stage IV melanoma. A parallel placebo-controlled study has been conducted to further assess the efficacy of lenalidomide in stage IV melanoma patients.

25 Clinical Trial Phase 2 open-label study of weekly docosahexaenoic acid-paclitaxel in cutaneous and mucosal metastatic melanoma patients. 2009

Homsi, Jade / Bedikian, Agop Y / Kim, Kevin B / Papadopoulos, Nicholas E / Hwu, Wen-Jen / Mahoney, Sandy L / Hwu, Patrick. ·Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, 1515 Holcombe Building, Unit 430, Houston, TX 77030, USA. jhomsi@mdanderson.org ·Melanoma Res · Pubmed #19521262.

ABSTRACT: Docosahexaenoic acid (DHA)-paclitaxel has a unique pharmacokinetic profile that allows high concentrations of paclitaxel to be delivered to melanoma cells for prolonged periods compared with paclitaxel. We investigated the response rate and safety of weekly DHA-paclitaxel in metastatic melanoma patients. We enrolled chemotherapy-naive patients with metastatic nonchoroidal melanoma using the two-stage Fleming design. At least one response was needed in the first stage to proceed to the second stage. DHA-paclitaxel (500 mg/m/week by 1-h intravenous infusion) was administered for 5 weeks every 6-week cycle until disease progression, intolerable toxicity, or treatment refusal. Response and toxicity were assessed every 6 weeks and weekly, respectively. Thirty patients were enrolled. The patients' median age was 67 years (range: 29-86 years). The median number of treatment cycles was 2 (range: 1-6 cycles). Three patients (10%) had partial responses; one lasted 4 months, and two lasted 5.6 months. Fifteen patients (50%) had stable disease with a median duration of 2.8 months (range: 2.6-8.9 months). The median survival was 14.8 months. Neutropenia (10%) and musculoskeletal pain (10%) were the most common grade 3 and 4 toxicities, and fatigue (73%), skin rash (70%), and diarrhea (60%) were the most common side effects. As a single-agent therapy, DHA-paclitaxel was well tolerated in metastatic melanoma patients. Its efficacy as a first-line therapy for metastatic melanoma does not exceed that seen with other single-agent chemotherapies such as dacarbazine. Further evaluation of DHA-paclitaxel in combination with other chemotherapy or targeted agents could be considered.

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