Management of metastatic cutaneous melanoma.
The results of treatment for metastatic melanoma remain disappointing. Single-agent chemotherapy produces response rates ranging from 8% to 15%, and combination chemotherapy, from 10% to 30%. However, these responses are usually not durable. Immunotherapy, particularly high-dose interleukin (IL)-2 (Proleukin), has also shown a low response rate of approximately 15%, although it is often long-lasting. In fact, a small but finite cure rate of about 5% has been reported with high-dose IL-2. Phase II studies of the combination of cisplatin-based chemotherapy with IL-2 and interferon-alfa, referred to as biochemotherapy, have shown overall response rates ranging from 40% to 60%, with durable complete remissions in approximately 8% to 10% of patients. Although the results of the phase II single-institution studies were encouraging, phase III multicenter studies have reported conflicting results, which overall have been predominantly negative. Various factors probably explain these discrepancies including different biochemotherapy regimens, patient selection, and, most importantly, "physician selection." Novel strategies are clearly needed, and the most encouraging ones for the near future include high-dose IL-2 in combination with adoptive transfer of selected tumor-reactive T cells after nonmyeloablative regimens, BRAF inhibitors in combination with chemotherapy, and the combination of chemotherapeutic agents and biochemotherapy with oblimersen sodium (Genasense).
Buzaid
Antonio C
AC
Oncology Center, Hospital Sirio-Libanes, São Paulo, Brazil. buzaid@attglobal.net
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000008:administration & dosage; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D015337:Multicenter Studies as Topic; D009367:Neoplasm Staging; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D000077204:Temozolomide; D013873:Thionucleotides / Q000008:administration & dosage; D016896:Treatment Outcome
D007376:Interleukin-2; D013873:Thionucleotides; D003606:Dacarbazine; C408162:oblimersen; D002945:Cisplatin; D000077204:Temozolomide