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Phase I study of temozolomide and escalating doses of oral etoposide for adults with recurrent malignant glioma.

Publication ,  Journal Article
Korones, DN; Benita-Weiss, M; Coyle, TE; Mechtler, L; Bushunow, P; Evans, B; Reardon, DA; Quinn, JA; Friedman, H
Published in: Cancer
April 15, 2003

BACKGROUND: Although temozolomide is active against recurrent malignant glioma, responses in many patients are modest and short-lived. Temozolomide may prove more effective in combination with other agents. Therefore, combination oral chemotherapy for these patients is a particularly attractive approach. METHODS: The authors conducted a Phase I study of temozolomide in combination with escalating doses of oral etoposide (VP-16) to determine the maximum tolerated doses of these two agents when given together. The temozolomide dose was fixed at 150 mg/m(2) per day on Days 1-5. The oral VP-16 was escalated in cohorts of 3 to 6 patients by numbers of days of VP-16 administered: 50 mg/m(2) per day, Days 1-5 (dose level 1), Days 1-8 (dose level 2), Days 1-12 (dose level 3), Days 1-16 (dose level 4), and Days 1-20 (dose level 5). Therapy was given in 28-day cycles. RESULTS: Of the 29 patients enrolled, 26 were fully evaluable and 3 were partially evaluable for toxicity. The 29 patients received a total of 92 cycles. The median age of the patients was 49 years (range, 28-76 years). Diagnoses included glioblastoma (n = 19), gliosarcoma (n = 3), anaplastic astrocytoma (n = 5), and anaplastic oligoastrocytoma (n = 2). The median time from diagnosis to disease recurrence was 8 months (3-188 months). Twenty patients were treated at the first disease recurrence, seven at the second, and two at the third. Twenty-four patients (83%) were receiving anticonvulsants and 24 were receiving dexamethasone. All patients had received previous radiation, and 25 of 29 had been treated with chemotherapy previously. Of the 3 patients at dose level 1, none had dose-limiting toxicity (DLT). Of the 6 patients at dose level 2, 1 patient had DLT: Grade 3 thrombocytopenia resulting in a > 2-week delay in starting the next cycle of chemotherapy. Of the 6 patients at dose level 3, 1 patient had DLT: death due to pneumonia. There were 2 DLTs in the 7 patients at dose level 4: fever, neutropenia, and herpes zoster infection in 1 patient and death due to pneumonia in another. Seven patients had been started at dose level 5 when DLT was established at dose level 4: of the 5 fully evaluable and 2 partially evaluable patients at dose level 5, there was no DLT. CONCLUSIONS: The maximum tolerated dose of temozolomide and oral VP-16 in this heavily treated group of patients with recurrent malignant glioma is temozolomide 150 mg/m(2) per day for 5 days and oral VP-16 50 mg/m(2) per day for 12 days.

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Published In

Cancer

DOI

ISSN

0008-543X

Publication Date

April 15, 2003

Volume

97

Issue

8

Start / End Page

1963 / 1968

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Temozolomide
  • Survival Rate
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Maximum Tolerated Dose
  • Male
  • Humans
  • Glioma
 

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Korones, D. N., Benita-Weiss, M., Coyle, T. E., Mechtler, L., Bushunow, P., Evans, B., … Friedman, H. (2003). Phase I study of temozolomide and escalating doses of oral etoposide for adults with recurrent malignant glioma. Cancer, 97(8), 1963–1968. https://doi.org/10.1002/cncr.11260
Korones, David N., Michal Benita-Weiss, Thomas E. Coyle, Laszlo Mechtler, Peter Bushunow, Brandon Evans, David A. Reardon, Jennifer A. Quinn, and Henry Friedman. “Phase I study of temozolomide and escalating doses of oral etoposide for adults with recurrent malignant glioma.Cancer 97, no. 8 (April 15, 2003): 1963–68. https://doi.org/10.1002/cncr.11260.
Korones DN, Benita-Weiss M, Coyle TE, Mechtler L, Bushunow P, Evans B, et al. Phase I study of temozolomide and escalating doses of oral etoposide for adults with recurrent malignant glioma. Cancer. 2003 Apr 15;97(8):1963–8.
Korones, David N., et al. “Phase I study of temozolomide and escalating doses of oral etoposide for adults with recurrent malignant glioma.Cancer, vol. 97, no. 8, Apr. 2003, pp. 1963–68. Pubmed, doi:10.1002/cncr.11260.
Korones DN, Benita-Weiss M, Coyle TE, Mechtler L, Bushunow P, Evans B, Reardon DA, Quinn JA, Friedman H. Phase I study of temozolomide and escalating doses of oral etoposide for adults with recurrent malignant glioma. Cancer. 2003 Apr 15;97(8):1963–1968.
Journal cover image

Published In

Cancer

DOI

ISSN

0008-543X

Publication Date

April 15, 2003

Volume

97

Issue

8

Start / End Page

1963 / 1968

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Temozolomide
  • Survival Rate
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Maximum Tolerated Dose
  • Male
  • Humans
  • Glioma