A phase II study of oxaliplatin, docetaxel, and GM-CSF in patients with previously treated advanced melanoma
- 141 Downloads
Although much focus has been placed on immunotherapy for melanoma, further development of chemotherapy approaches is needed. Melanoma is responsive to platinum compounds and taxanes, but there is limited experience with combinations of these agents. Oxaliplatin has been reported to have detectable activity in melanoma, and a phase I study has identified a tolerable dose and schedule of oxaliplatin in combination with docetaxel and hematopoietic growth factor support. GM-CSF has a theoretical advantage of immune potentiation. These considerations supported the study of oxaliplatin, docetaxel, and GM-CSF in patients with advanced melanoma.
Eligibility included adequate organ function, PS ≤ 2, at most one prior chemotherapy and one prior immunotherapy, no prior treatment with oxaliplatin or taxanes and no chremophor allergy. After premedication, docetaxel was administered day 1 at 75 mg/m2, then oxaliplatin on day 2 at 85 mg/m2. GM-CSF (250 mcg/m2) was administered s.c. days 3–12. Cycles were 21 days in length, and disease reevaluation was performed every two cycles by RECIST criteria.
Nineteen patients received at least one cycle, eight with one prior systemic therapy, five with two prior systemic therapies. Five patients did not complete two cycles and were not formally evaluable for response. Five patients had stable disease (SD), including one who failed two prior therapies and went on to receive ten cycles. The remaining nine patients displayed progressive disease (PD) after two cycles. Notable toxicities included seven cases (37%) of grade III/IV neutropenia and two (11%) hypersensitivity reactions.
This combination of oxaliplatin, docetaxel, and GM-CSF has limited clinical activity in previously treated patients with advanced melanoma. Exploration in treatment-naïve patients may still be warranted.
KeywordsMelanoma Metastatic Oxaliplatin Docetaxel GM-CSF Chemotherapy
- 1.Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, Abrams J, Sznol M, Parkinson D, Hawkins M, Paradise C, Kunkel L, Rosenberg SA (1999) High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 17:2105–2116PubMedGoogle Scholar
- 3.Patel PM (2008) Extended schedule, escalated dose temozolomide versus dacarbazine in stage IV malignant melanoma final results of the randomized phase III study (EORTC 18032). In: 33rd congress of the European Society for Medical OncologyGoogle Scholar
- 5.Korn EL, Liu PY, Lee SJ, Chapman JA, Niedzwiecki D, Suman VJ, Moon J, Sondak VK, Atkins MB, Eisenhauer EA, Parulekar W, Markovic SN, Saxman S, Kirkwood JM (2008) Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol 26:527–534CrossRefPubMedGoogle Scholar
- 8.Chapman PB, Einhorn LH, Meyers ML, Saxman S, Destro AN, Panageas KS, Begg CB, Agarwala SS, Schuchter LM, Ernstoff MS, Houghton AN, Kirkwood JM (1999) Phase III multicenter randomized trial of the Dartmouth regimen versus dacarbazine in patients with metastatic melanoma. J Clin Oncol 17:2745–2751PubMedGoogle Scholar
- 18.Bissery MC, Vrignaud P, Lavelle F (1995) Preclinical profile of docetaxel (taxotere): efficacy as a single agent and in combination. Semin Oncol 22:3–16Google Scholar
- 19.Kouroussis C, Agelaki S, Mavroudis D, Kakolyris S, Androulakis N, Kalbakis K, Souglakos J, Mallas K, Bozionelou V, Pallis A, Adamtziki H, Georgoulias V (2003) A dose escalation study of docetaxel and oxaliplatin combination in patients with metastatic breast and non-small cell lung cancer. Anticancer Res 23:785–791PubMedGoogle Scholar
- 24.Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216CrossRefPubMedGoogle Scholar
- 26.Legha SS, Ring S, Eton O, Bedikian A, Buzaid AC, Plager C, Papadopoulos N (1998) Development of a biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, dacarbazine, interferon alfa, and interleukin-2 for patients with metastatic melanoma. J Clin Oncol 16:1752–1759PubMedGoogle Scholar
- 27.Eton O, Legha SS, Bedikian AY, Lee JJ, Buzaid AC, Hodges C, Ring SE, Papadopoulos NE, Plager C, East MJ, Zhan F, Benjamin RS (2002) Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results from a phase III randomized trial. J Clin Oncol 20:2045–2052CrossRefPubMedGoogle Scholar
- 28.Keilholz U, Punt CJ, Gore M, Kruit W, Patel P, Lienard D, Thomas J, Proebstle TM, Schmittel A, Schadendorf D, Velu T, Negrier S, Kleeberg U, Lehman F, Suciu S, Eggermont AM (2005) Dacarbazine, cisplatin, and interferon-alfa-2b with or without interleukin-2 in metastatic melanoma: a randomized phase III trial (18951) of the European Organisation for Research and Treatment of Cancer Melanoma Group. J Clin Oncol 23:6747–6755CrossRefPubMedGoogle Scholar
- 29.Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, Seipp CA, Einhorn JH, White DE, Steinberg SM (1999) Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b. J Clin Oncol 17:968–975PubMedGoogle Scholar
- 30.Atkins MB, Hsu J, Lee S, Cohen GI, Flaherty LE, Sosman JA, Sondak VK, Kirkwood JM (2008) Phase III trial comparing concurrent biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b with cisplatin, vinblastine, and dacarbazine alone in patients with metastatic malignant melanoma (E3695): a trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 26:5748–5754CrossRefPubMedGoogle Scholar
- 33.Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, Mulligan RC (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 90:3539–3543CrossRefPubMedGoogle Scholar
- 37.Gamelin L, Boisdron-Celle M, Delva R, Guerin-Meyer V, Ifrah N, Morel A, Gamelin E (2004) Prevention of oxaliplatin-related neurotoxicity by calcium and magnesium infusions: a retrospective study of 161 patients receiving oxaliplatin combined with 5-Fluorouracil and leucovorin for advanced colorectal cancer. Clin Cancer Res 10:4055–4061CrossRefPubMedGoogle Scholar