Cisplatin and carboplatin combination as second-line chemotherapy in dacarbazine-resistant melanoma patients

Abstract

High-dose cisplatin regimens have been shown to be highly active in advanced melanoma patients but are associated with unacceptable side effects. In order to increase the platinum dose but avoid severe side effects, we treated 15 dacarbazine (DTIC)-resistant metastatic melanoma patients with a combination regimen of cisplatin (100 mg/m2) and carboplatin (200 mg/m2), two platinum analogues with a similar mode of action but a different toxicity pattern. After a mean follow-up period of 10.7 months (range 4-18 months), two patients (13.3%) achieved complete remission and two patients (13.3%) showed partial remission, giving an overall response rate of 26.4% (95% confidence interval [CI] 4.2-49%). Furthermore, three patients (20%; 95% CI 0-40.2%) experienced stable disease. The median duration of response was 7.1 months (95% CI 4.2-10.0 months), and the median overall survival was 12.5 months (95% CI 5.8-19.2 months), with eight patients still alive. The main side effects were haematological (leukopenia/thrombocytopenia World Health Organization [WHO] grade I-IV; anaemia WHO grade I-III), gastrointestinal (WHO grade I-III), neurological (WHO grade I-II) and renal (WHO grade I) toxicity. Nevertheless, except in one patient, side effects did not result in discontinuation of therapy. Despite the small number of patients treated in this preliminary study, we believe that combining cisplatin and carboplatin represents a novel, active and well-tolerated therapeutic option as second-line chemotherapy in DTIC-resistant advanced melanoma patients.

High-Dose Platinum Combination Therapy in Pretreated Patients with Disseminated Melanoma

“…We found 50% of the patients with SD. Comparable results with this therapeutic regimen have been reported by Guven et al [16] with objective response rates of 26% and a median survival of 7.1 months. Their results in conjunction with our independent confirmation in a much larger group of patients seem to indicate a beneficial effect for the combination of cisplatin and carboplatin.…”

“…In a small study, the combination of cisplatin and carboplatin was well tolerated and showed favourable response rates and a possible impact on overall survival in dacarbazine-resistant patients with disseminated melanoma [16] . Second-line studies are needed, but are rare in melanoma patients.…”

“…Only one study [16] was performed in 15 dacarbazine-resistant melanoma patients with an overall response rate of 26.4% and an overall median survival of 12.5 months. This combination potentially offers patients with advanced malignant melanoma an improvement in efficacy with an acceptable toxicity profile.…”

Organotin(IV)‐Loaded Mesoporous Silica as a Biocompatible Strategy in Cancer Treatment

“…[4] The goal in developing new metal-based anticancer drugs is to overcome the main limitations of cisplatin, such as its narrow range of activity, the development of resistance, and its severe toxicity. [5] Apoptosis is the basic mechanism of the anticancer action of numerous chemotherapeutics.…”

Adjuvant Therapy of Uveal Melanoma: Current Status

“…Platinum compounds, which cross-link DNA, are considered to be among the more active cytotoxic chemotherapeutics in melanoma [17]. Sunitinib inhibits receptor tyrosine kinases, which signal through several pathways, including the MAPK pathway.…”