Metronomic schedule of temozolomide with conventional dose of cisplatin in metastatic melanoma. Sub-category: Melanoma Categor

Sub-category: Melanoma

Category: Melanoma

Meeting: 2009 ASCO Annual Meeting

Citation: J Clin Oncol 27, 2009 (suppl; abstr e20009)

Abstract No: e20009'

Author(s): E. Simeone, A. Daponte, G. De Feo, V. Montesarchio, V. Chiarion-Sileni, I. De Michele, C. Caracò, G. Palmieri, N. Mozzillo, P. A. Ascierto; Istituto Nazionale Tumori Pascale, Naples, Italy; Azienda Ospedaliera Cotugno, Napoli, Italy; Istituto Oncologico Veneto, Padova, Italy; Institute of Biomolecular Chemistry-CNR, Sassari, Italy

Abstract:

Background: Dacarbazine (DTIC) is the standard treatment for metastatic melanoma. Temozolomide (TMZ) is a potentially attractive chemotherapeutic agent for this disease because of the oral route of administration and efficacy similar to that of dacarbazine. Cisplatin is active against melanoma and might counteract mechanisms of resistance to TMZ. Metronomic administration of TMZ might be another way to overcome resistance.

Patients and Methods: We reviewed data of metastatic melanoma patients treated at our Institutions with cisplatin (75 mg/m² every 28 days) plus TMZ (75 mg/m²/die from day 2 for 21 days). Our practice included such scheme for patients younger than 75 years, with a performance status not worse than 2, and adequate bone marrow, liver and renal function. Assessment of response was done every 3 cycles. Toxicity was graded according to NCI-CTC.

Results: From August 2007 to September 2008, 33 patients were treated with a median age of 44 years (18-74); primary melanoma was ulcerated in 19 cases (58%); most frequent sites of metastases were lung (18 cases), brain and lymph nodes (11 cases each); 29 patients were treated as first-line and 4 as second-line. The median number of delivered cycles was 4 (range 2- 8). Toxicity was mild, with no grade 4 event reported. Nausea and vomiting were the most frequent and severe toxic effects: grade 3 in 2 cases each and grade 2 in 16 and 9 cases, respectively. Other toxicities included thrombocytopenia (2 case grade 3 and 3 cases grade 2), anemia (1 grade 3 and 4 grade 2), neutropenia, and fatigue (1 grade 3 each). Overall, 6 patients had a partial response (18.2%; 95% exact CI: 7.0-35.5) and 8 (24%) had a disease stabilization. With a median follow-up of 20 weeks (95% CI: 19-57), there were 19 progressions and a median progression-free survival of 24 weeks (95% CI:16-nr); 9 patients died with a median survival of 50 weeks (95% CI 43-nr).

Conclusions: Results obtained in clinical practice with metronomic temozolomide plus cisplatin in the treatment of patients with metastatic melanoma are encouraging, in light of the negative prognostic features of treated patients. We are now planning a formal phase II study.