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Single-agent chemotherapy of brain tumors. A five-year review
Abstract:
Identification of effective single chemotherapeutic agents for brain tumors must precede the rational use of multiple drug combinations. In phase 2 trials beginning in 1968, 158 patients with intrinsic brain tumors (mostly recurrent malignant astrocytomas) were considered evaluable. The larger trials with more effective drugs produced these results: carmustine (BCNU) response rate, 47%, with median duration of nine months; lomustine (CCNU), 44%, with median duration of six months; procarbazine hydrochloride, 52%, with median duration six months; carmustine and vincristine sulfate combined, 44%, with median duration of only four months; and BIC (5-[3,3-bis(2-chloroethyl)-1-triazeno]imidazole-4-carboxamide), 38%, with median duration of five months. Administration of glucocorticoids was not found to bias the frequency of response. Forty-seven patients, 26 of whom had responded to the initial drug, received a second drug. Among 26 patients who were evaluable, only four responded to the second drug.
Insights
Effective single chemotherapy drugs for brain tumors like malignant astrocytomas were identified. Procarbazine showed a 52% response rate, but combination therapies offered limited added benefit and shorter durations.
Area of Science:
- Neuro-oncology
- Clinical Pharmacology
Background:
- Effective single chemotherapeutic agents are crucial for developing rational combination therapies for brain tumors.
- Phase 2 trials are essential for evaluating novel treatment strategies.
Purpose of the Study:
- To identify effective single chemotherapeutic agents for intrinsic brain tumors, primarily recurrent malignant astrocytomas.
- To evaluate the efficacy and duration of response for various single-agent and combination chemotherapy regimens.
Main Methods:
- Phase 2 clinical trials involving 158 evaluable patients with intrinsic brain tumors.
- Assessment of response rates and median duration of response for carmustine (BCNU), lomustine (CCNU), procarbazine hydrochloride, BIC, and carmustine/vincristine combinations.
- Evaluation of sequential drug administration in patients who initially responded to treatment.
Main Results:
- Procarbazine hydrochloride demonstrated the highest response rate (52%) with a median duration of six months.
- Carmustine (BCNU) showed a 47% response rate (median duration nine months), lomustine (CCNU) 44% (median duration six months), and BIC 38% (median duration five months).
- Combination therapy with carmustine and vincristine sulfate yielded a 44% response rate but a shorter median duration of four months. Sequential administration of a second drug showed limited efficacy, with only 4 out of 26 evaluable patients responding.
Conclusions:
- Procarbazine hydrochloride emerged as a highly effective single agent for intrinsic brain tumors.
- Combination chemotherapy did not significantly improve response rates and potentially reduced response duration compared to effective single agents.
- Sequential chemotherapy offers limited benefit for patients who do not respond to or relapse after initial treatment.