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

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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
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
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).
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.