New Salvage Regimen for Glioma Shows Promise

HONOLULU—Salvage therapy with cisplatin (Platinol), etoposide (VP-16), and vincristine (CVV) for recurrent malignant gliomas has moderate activity that may lead to long-term stabilization in heavily pretreated patients, according to H. Lee Moffitt investigators who presented their findings at the 55th Annual Meeting of the American Academy of Neurology (abstract P01.001).

A number of patients, particularly those with anaplastic astrocytoma or anaplastic oligodendroglioma, have achieved sustained remission, and a few are still alive some 4 years after treatment with this regimen, said Surasak Phuphanich, MD, professor of neurology and oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.

From 1998 to 2002, the researchers enrolled 64 patients (median age, 51), with glioblastoma multiforme (n = 44), anaplastic astrocytoma (n = 12), and anaplastic oligodendroglioma (n = 8). Patients received cisplatin 100 mg/m² on day 1, etoposide 100 mg/m² on days 1 to 3, and vincristine 1.5 mg/m² on day 1, in a 4-week cycle for a maximum of eight cycles. Patients were evaluated by neurological exam and MRI every 8 weeks.

Patients had undergone previous surgery, radiation therapy, and up to four chemotherapy or biotherapy regimens. Twenty-five patients (39%) had undergone more than two prior chemotherapy regimens. The most common regimens were BCNU (carmustine)/Gliadel wafer, PCV (procarbazine, CCNU, vincristine), and temozolomide (Temodar).

In some cases, the response was substantial. Dr. Phuphanich described one patient with a 5-cm lesion recurring after surgery that shrank by 90% after the CVV regimen ( see Figure ). About 25% of his patients may achieve this degree of response, he said.

Two anaplastic astrocytoma patients who achieved a durable complete response did not have previous chemotherapy, indicating that this regimen may be of value earlier in the treatment algorithm. "For these two patients, the tumor completely disappeared, and they have been tumor free for about 10 months," he reported. "That is why we believe this regimen will be most useful upfront, instead of salvage, in the future."

Time to tumor progression was 19 weeks for glioblastoma multiforme and 60 weeks for anaplastic astrocytoma/anaplastic oligodendroglioma. Two patients are still in complete remission more than 202 weeks and 242 weeks post-treatment.

Median survival was 36.5 weeks for glioblastoma multiforme, with four patients alive at 42+, 66+, 86+, and 196+ weeks. For the anaplastic astrocytoma/anaplastic oligodendroglioma subset, median survival was 80 weeks, and six patients are still alive at 49+, 51+, 66+, 199+, 202+, and 242+ weeks, he said.

Hematologic toxicity higher than grade 2 occurred in 22% of patients, including 28% with mild hearing loss and 16% with sensory peripheral neuropathy. One patient developed renal failure after two cycles of treatment.