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Phase II studies of mitozolomide in melanoma, lung and ovarian cancer
M Harding1, V Docherty, R Mackie
1Department of Medical Oncology, University of Glasgow, U.K.
Abstract:
Seventy-seven patients were treated with oral mitozolomide to assess the activity of this drug in melanoma, lung and ovarian cancer. Partial responses were seen in five of 18 evaluable patients with small cell lung cancer (SCLC) and three of 20 with melanoma. No activity was apparent in non small cell lung or epithelial ovarian cancer. The major toxicity was myelosuppression which necessitated reduction in the initial dosage from 115 to 90 mg/m2. However, even at this dose level, unpredictable WHO grade 4 toxicity occurred in non-pretreated patients. Thrombocytopenia was more common than leucopenia and eight patients required platelet transfusion for spontaneous or tumour-related haemorrhage. Myelotoxicity was considered responsible for two deaths and was a significant contributory factor in a further three. Non-haematological toxicity was minor. Thus, despite demonstrable activity in SCLC and melanoma, unpredictable myelosuppression is likely to preclude further assessment in combination chemotherapy regimes in these tumours.
Insights
Oral mitozolomide showed activity in small cell lung cancer (SCLC) and melanoma but caused significant myelosuppression. Unpredictable severe toxicity, including fatal cases, limits its use in combination chemotherapy.
Area of Science:
- Oncology
- Pharmacology
Background:
- Mitozolomide is an oral alkylating agent.
- Its efficacy and toxicity profile in various cancers require evaluation.
Purpose of the Study:
- To assess the activity of oral mitozolomide in melanoma, lung cancer, and ovarian cancer.
- To evaluate the toxicity of oral mitozolomide.
Main Methods:
- Seventy-seven patients with advanced cancers received oral mitozolomide.
- Activity and toxicity were monitored using standard clinical and laboratory assessments.
Main Results:
- Partial responses were observed in 5/18 patients with small cell lung cancer (SCLC) and 3/20 with melanoma.
- No significant activity was noted in non-small cell lung cancer or epithelial ovarian cancer.
- The primary toxicity was myelosuppression, leading to dose reduction and unpredictable Grade 4 events, including fatal cases.
Conclusions:
- Oral mitozolomide demonstrates activity in SCLC and melanoma.
- Severe and unpredictable myelosuppression limits its use, particularly in combination chemotherapy regimens.