Prolonged response without prolonged chemotherapy: a lesson from PCV chemotherapy in low-grade gliomas

Abstract

Previous studies with temozolomide suggest that a prolonged duration of chemotherapy is important for treating low-grade gliomas (LGGs). PCV (procarbazine, CCNU, vincristine) chemotherapy has demonstrated efficacy in treating LGGs, but this therapy cannot be used for a prolonged period because of the cumulative toxicity. The aim of the present study was to evaluate the impact of first-line PCV chemotherapy on LGGs growth kinetics. The mean tumor diameter (MTD) of 21 LGGs was measured on serial magnetic resonance images before (n=13), during, and after PCV onset (n=21). During PCV treatment, a decrease in the MTD was observed in all patients. After PCV discontinuation, an ongoing decrease in MTD was observed in 20 of the 21 patients. Median duration of the MTD decrease was 3.4 years (range, 0.8-7.7) after PCV onset and 2.7 years (range, 0-7) after the end of PCV treatment with 60% of LGGs, demonstrating an ongoing and prolonged (>2 years) response despite chemotherapy no longer being administered. According to McDonald's criteria, the rates of partial and minor responses were 5% and 38% at the end of PCV but 38% and 42% at the time of maximal MTD decrease, which occurred after a median period of 3.4 years after PCV onset. These results challenge the idea that a prolonged duration of chemotherapy is necessary for treating LGGs and raise the issue of understanding the mechanisms involved in the persistent tumor volume decrease once chemotherapy is terminated.

Fig. 1.

Evolution of the mean tumor diameter (MTD) before, during, and after PCV chemotherapy. The evolution of the MTD of each patient before (n = 13), during (n = 21), after (n = 21), and at progression (n = 14) is shown in blue, green, red, and yellow, respectively. During PCV chemotherapy, a decrease in the MTD (green curves) was observed in all patients. After PCV chemotherapy discontinuation, except in one patient (the patient with the smallest MTD at PCV onset), a persistent decrease in the MTD was observed in all patients (red curves).

Fig. 2.

Examples of the ongoing decrease in LGG volume in 2 patients observed after PCV discontinuation. Evolution of MRI scans in 2 patients: at diagnosis (A and E), before PCV onset (B and F), at the end of PCV treatment (C and G), and at the time of maximal response (D and H), with corresponding evolution of the MTD and MTD growth rate (mm/year). The patient on the left (A, B, C, and D) received only 2 cycles because of hematological toxicity; the patient on the right (E, F, G, and H) received 6 cycles. The time period in gray corresponds to the duration of PCV chemotherapy. On the left curve, a proposed mechanism to explain the persistent volume decrease following the discontinuation of PCV chemotherapy is shown.