TMZ at this dose and schedule results in CD4(+) lymphopenia in a majority of patients that can result in OIs. Pneumocystis pneumonia prophylaxis should be considered for patients who develop sustained lymphopenia on TMZ.

The combination of temozolomide plus thalidomide seems to be a promising and well-tolerated oral regimen for metastatic melanoma that merits further study.

Temozolomide (TMZ) is an oral alkylating agent with a good safety profile and proven efficacy in the treatment of malignant glioma. Procarbazine (PCB) has been used for treating gliomas for many years and here both agents were combined in the treatment. This phase I study was designed to evaluate the efficacy and safety of TMZ alone (course 1) and TMZ in combination with PCB in subsequent courses in chemotherapy-naïve patients with malignant glioma. Patients with anaplastic astrocytoma (AA), glioblastoma multiforme (GBM) and low-grade glioma were treated with TMZ 200 mg m À2 on days 1 -5 on a 28-day cycle for course 1. Beginning with course 2, cohorts of patients received TMZ at full dose with escalating doses of PCB (50/75/100/125 mg m À2 days 1 -5 given 1 h prior to TMZ). A total of 28 patients were enrolled with three patients each at dose level 1 and 2, 16 patients at dose level 3 and six patients at dose level 4 received 182 þ cycles of treatment and were included in this analysis. In all, 16 patients had GBM, seven patients had AA, five had grade 1 or 2 glioma and the median age was 47 years. The patients had received prior surgery and radiotherapy. Responses were seen at all dose levels. Overall, there were 10 (36%) responses lasting from 2 to 17 þ months. Treatment was generally well tolerated with few grade 3 or 4 toxicities, except at dose level 4, where four patients had grade 3/4 had thrombocytopaenia at this dose and several patients had moderate-to-severe lethargy. TMZ 200 mg m À2 and PCB 100 mg m À2 were well tolerated on a daily 5 Â and four weekly cycle in patients with malignant glioma and clearly had antitumour activity. Prognosis with patients with glioma, and in particular, high-grade (anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM)) tumours is poor. Studies have confirmed the beneficial effect of postoperative cranial irradiation, but in most series, survival beyond 2 years is 15% or less (Walker et al, 1978;Stewart, 1989;Fine et al, 1993). The most widely used combination in treating gliomas is procarbazine, CCNU (lomustine), vincristine (PCV). This has a limited effect on survival (Levin et al, 1980;Sandberg-Wollheim et al, 1991). The most active agents identified until recently were the nitrosoureas (BCNU, CCNU, methyl-CCNU and HECNU), and have been reported to induce responses in the range of 35 -55%. However, the majority of these responses were of short duration (Rodriguez and Levin, 1987;Georges et al, 1988;Stewart, 1989).Temozolomide came from a synthetic programme of a number of imidazotetrazine derivatives, which exhibited broad-spectrum antitumour activity against murine models (Stevens et al, 1984). TMZ was selected for further clinical development in view of its good experimental antitumour activity and low toxicity in the pre-clinical screen. In addition, its antitumour activity was also schedule-dependent (Stevens et al, 1987). In the early clinical development of TMZ, administration of a single dose induced myelosupression but did not have any antitumour activi...

We evaluated the sequential use of carboplatin, paclitaxel and topotecan in patients with advanced, previously untreated ovarian cancer. In total, 43 patients with advanced ovarian cancer and 41 cm residual disease were treated with sequential carboplatin (areaunder-the-curve (AUC) 5 days 1 and 22), paclitaxel (175 mg m À2 days 43 and 64) and topotecan (1.5 mg m À2 daily for 5 days from days 85, 106, 127 and 148). Median age of patients was 61 years. Median follow-up was 22.2 months (range 0.76 -50.6 months). In all, 34 (79%) patients received all eight cycles of treatment and nine (21%) withdrew. Of the 29 evaluable patients, 19 (66%) responded according to WHO and 30 of 36 (83%) patients according to CA125. The best overall response (CA125 and/or WHO) was 77% (33 of 43 patients). The response rates to sequential drugs based on 450% fall in CA125 were as follows: carboplatin, 77% (30 of 39 patients); paclitaxel, 65% (15 of 23 patients); topotecan, 38% (five of 13 patients). Two patients responded to paclitaxel and one to topotecan after failure to respond to preceding chemotherapy. Median survival and time to progression was 22.24 and 10.61 months, respectively. This study demonstrates that sequential chemotherapy with just two initial courses of carboplatin is a reasonable way to introduce new agents into first-line therapy for poor prognostic ovarian cancer patients.