IA chemotherapy approaches utilizing multiple IA agents or the combination of an IA agent with an oral or intravenous drug have also been extensively reported in the literature (see Table 17.4). The majority of regimens have focused on the use of IA carmustine in combination with other drugs. The initial experience was reported by West and colleagues, when they utilized a regimen of IA carmustine (100 mg/m2) plus PCV for nine patients with recurrent malignant gliomas . The objective response rate was 22 per cent, with a median survival of 20 weeks. Neurotoxicity was similar to that reported above for IA carmustine. Another report combined IA carmustine (100-125 mg/m2), IA cisplatin (60 mg/m2), and IA teniposide (VM-26; 150-175 mg/m2) in a series of 19 patients . The response rate was 68 per cent, with another 6 per cent stabilizing while on treatment. However, the overall median TTP was only 15 weeks. The regimen was limited by retinal toxicity (19 per cent), hearing loss (5 per cent), and neurological deterioration (19 per cent); toxicity data included patients with brain metastases. A similar study by Kapp and co-workers combined IA carmustine (300 mg) and cisplatin (150-200 mg) with oral lomustine . A series of 13 patients were treated, with an objective response rate of 62 per cent and another 23 per cent with SD. The median TTP was 36 weeks, with a median survival of 44 weeks. Although retinal toxicity was mild, there was a significant proportion of patients with neurological deterioration (38 per cent). In a follow-up study by Stewart and associates, a very aggressive regimen was attempted that included IA carmustin, cisplatin, and teniposide, as well as systemic bleomycin, vincristine, methotrexate, and procarbazine . A cohort of 22 patients received the regimen, with an objective response rate of 52 per cent. There was a median TTP for responders of 19 weeks and an overall median survival of only 21 weeks. Neurological and systemic toxicity were considerable, and included neurological deterioration (31 per cent) and pulmonary fibrosis. The authors concluded that the addition of systemic chemotherapy did not improve efficacy in comparison to IA carmustine, cisplatin, and teniposide alone. In another aggressive approach, IA carmustine (300-400 mg) and IA cisplatin (150-200 mg) were administered in an alternating, sequential pattern (i.e., each drug x 2 doses, every 4-6 weeks) for a series of 43 patients with recurrent malignant gliomas . Due to
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