Carboplatin in small cell lung cancer.
The high activity of carboplatin as a single agent in small cell lung cancer was first identified in 30 previously untreated patients who had a 60% response, which included a 10% complete remission (CR). In this and subsequent studies, carboplatin showed high activity without the nephrotoxicity and neurotoxicity associated with cisplatin. Gastrointestinal side effects and alopecia were also generally mild; the major toxicity was myelosuppression. Two important studies of carboplatin 300 mg/m2 and etoposide (300 to 400 mg/m2) in divided doses have reported objective responses of 85% (21% CR) and 65% (21% CR) in previously untreated patients. However, the median survival in the first study was only 9.5 months in both limited- and extensive-stage patients. In this study, 19% of patients had substantial dose reductions because of myelosuppression. The second study reported a better median survival of 15.3 months for limited-stage patients and 8.3 months for extensive-stage patients. These patients received a maximum of six courses of chemotherapy as opposed to four in the first study, and cranial irradiation in addition to mediastinal irradiation. There also appeared to be fewer dose reductions, ie, 11% for carboplatin. Another study using the combination of carboplatin and etoposide in extensive-stage patients only reported a 56% response rate, including 16% CR and a median survival of 8.1 months. The major toxicity in these three studies was myelosuppression, particularly leukopenia, but only three neutropenia-associated deaths occurred in a total of 180 patients. A recent study has reported the use of similar doses of carboplatin and etoposide in combination with ifosfamide 5 g/m2 (with mesna) and midcourse vincristine. Thoracic radiotherapy was given after six courses of chemotherapy in responding patients, but no cranial irradiation was used. In 42 patients, 30 of whom had limited-stage disease, the response rate was 78%, including a 57% CR rate. The median survival was 14 months, and the 2-year actual survival rate is 33%. These and other studies of carboplatin combinations (which are only preliminary) have described high response rates and possibly improved survival compared with less intensive therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
Thatcher
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Cancer Research Campaign Department of Medical Oncology, Christie Hospital and Holt Radium Institute, Manchester, United Kingdom.
Lind
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D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D005047:Etoposide; D016190:Carboplatin