Although chemotherapy has been shown to delay the need for radiation therapy in the majority of patients with unresectable low-grade gliomas, the published CR rates for patients treated with the most commonly used chemotherapy regimens range from 0% to 5%.4,8–10
Long-term progression-free survival rates with chemotherapy alone are quite low and non–NF-1 patients with such tumors frequently receive more than 1 regimen of chemotherapy to delay the use of radiation for as long as possible. For patients with visual pathway gliomas, however, treatment with chemotherapy rarely results in significant recovery of vision, and many of these patients sustain significant visual impairment.11
The combination of carboplatin and vincristine is generally considered the standard frontline treatment for unresectable low-grade gliomas, as evidenced by the fact that all of the patients who had received prior chemotherapy in this trial had received carboplatin and vincristine. A randomized Children's Oncology Group study using a “pick the winner” design compared carboplatin/vincristine with TPCV (6-thioguanine, procarbazine, CCNU, and vincristine) and found that the 5-year event-free survival with carboplatin/vincristine was 34.6% ± 4.8% compared with a 48.9% ± 4.8% 5-year event-free survival with TPCV, casting doubt on whether carboplatin/vincristine should truly be considered the best standard regimen.12
Most oncologists do not utilize the TPCV regimen as frontline therapy largely because of the concern for adverse late effects in patients who are expected to have a reasonably long-term survival. Patients with NF-1, who frequently develop low-grade gliomas, are at particularly high risk for alkylator-related second malignancies,13
which limits the number of available regimens for these patients.
An alternative regimen used by many institutions in the United States and Europe consists of single-agent carboplatin administered monthly at a dose of 560 mg/m2
Toxicity with this regimen is quite tolerable; 85% of patients experienced disease stabilization or better for a median of 22 months.3
No randomized studies comparing single-agent carboplatin with carboplatin/vincristine have been undertaken, although the published disease stabilization and event-free survival rates are similar.3,8
Because the data for the efficacy of vincristine as a single agent against low-grade gliomas are obscure at best, it would seem rational to evaluate the combination of carboplatin with an agent with proven activity.
A recent clinical trial of single-agent vinblastine given weekly for a year demonstrated activity against recurrent and refractory low-grade gliomas.7
As of the most recent published follow-up, the study had enrolled 51 children with progressive low-grade gliomas following prior chemotherapy (n
= 50) and/or radiation therapy (n
= 9). Independent central radiology review of the first 31 patients confirmed 1 CR, 3 PRs, 9 MRs, 10 stable disease, and 10 progressive disease, with an overall response rate (CR + PR + MR) of 42%. Preclinical data showing that the antitumor activity of cytotoxic chemotherapeutic agents can be augmented by combining them with angiogenesis inhibitors14
also supports the rationale for this combination. Furthermore, vinblastine can be given at home with the assistance of personnel from a home care agency, decreasing the need for frequent clinic visits.
Our study found that the myelosuppressive effects of vinblastine can be limiting when this drug is combined with carboplatin. However, a reasonable alternative schedule proved tolerable, which allowed for 3 weekly doses of vinblastine combined with monthly carboplatin. The results were encouraging, with both radiographic and clinical responses seen. Objective responses were observed in both recurrent and newly diagnosed patients. However, given the small number of patients and the different dosing schedules, no conclusions can be drawn as to whether there was a higher response rate in newly diagnosed patients. A comparison of this regimen with others in terms of efficacy, toxicity, and convenience is warranted.