Combined Thalidomide and Temozolomide Treatment in Patients with Glioblastoma Multiforme
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Objectives: Glioblastoma multiforme (GBM) may potentially be responsive to antiangiogenic therapies as these tumors are highly vascularized and overexpress angiogenic factors. Thalidomide exhibits antiangiogenic activity and may provide additive or synergistic antitumor effects when given concurrently with temozolomide, an alkylating agent. To further evaluate this new concept of combining an antiangiogenic with an alkylating agent, efficacy and tolerability of thalidomide alone and in combination with temozolomide were explored in a single-institution, nonrandomized open-label phase II study.
Patients and methods: Forty-four patients with GBMs, who received thalidomide for a period of at least three months, were evaluated for survival, time to tumor progression (TTP), and side effects. Microsurgical tumor extirpation and radiotherapy preceded chemotherapy. Nineteen patients (43%) received thalidomide only (T), and 25 patients (57%) had a combined chemotherapy of thalidomide and temozolomide (TT). Median thalidomide dosage was 200 mg/day. Median temozolomide dosage was 200 mg/m2/day for five days, in monthly cycles. Neuroradiological outcomes were assessed by a semiquantitative grading system.
Results: Median survival was 103 weeks (95% CI, 65–141 weeks) for TT-patients and 63 weeks (95% CI, 49–77 weeks) for T-patients (p < 0.01). Median TTP for the TT-group was 36 weeks (95% CI, 20–52 weeks) and 17 weeks (95% CI, 13–21 weeks) for the T-group (p < 0.06). Neuroradiologically, 14 patients (56%) of the TT-group and six (32%) of the T-group had evidence of stable disease on at least two successive neuroradiological follow-ups. Progressive disease was found in nine patients (36%) of the TT-group and in 13 (68%) of the T-group. In two patients (8%) of the TT-group, a response with tumor regression was found. Thalidomide and concurrent temozolomide were safe and well tolerated with mild to moderate toxicities.
Conclusions: The combination of thalidomide and temozolomide in the treatment of GBM appears to be more effective than that of thalidomide alone with respect to survival, TTP, and neuroradiological documentation of progression, stable disease or response. Further concurrent prospective studies of these agents in a larger group of patients with GBM will be required to establish the soundness of these intriguing observations.
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- 1.Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K, Michael C, Miller D, Sawaya R: A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95: 190–198, 2001PubMedGoogle Scholar
- 4.Surawics TS, Davis F, Freels S, Laws ER Jr, Menck HR: Brain tumor survival: results from the National Cancer Data Base. J Neuro-Oncol 40: 151–160, 1998Google Scholar
- 9.Schiffer D, Chio A, Giordana MT, Mauro A, Migheli A, Vigliani MC: The vascular response to tumor infiltration in malignant gliomas. Morphometric and reconstruction study. Acta Neuropathol (Berl) 77: 369–378, 1989Google Scholar
- 16.Yung WK, Albright RE, Olson J, Fredericks R, Fink K, Prados MD, Brada M, Spence A, Hohl RJ, Shapiro W, Glantz M, Greenberg H, Selker RG, Vick NA, Rampling R, Friedman H, Phillips P, Bruner J, Yue N, Osoba D, Zaknoen S, Levin VA: A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer 83: 588–593, 2000CrossRefPubMedGoogle Scholar
- 17.Stupp R, Dietrich PY, Ostermann KS, Pica A, Maillard I, Maeder P, Meuli R, Janzer R, Pizzolato G, Miralbell R, Porchet F, Regli L, de Tribolet N, Mirimanoff RO, Leyvraz S: Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 20: 1375–1382, 2002CrossRefPubMedGoogle Scholar
- 22.Kleihues P, Burger PC, Collins VP, Newcomb EW, Ohgaki H, Cavanee WK: Pathology and Genetics: Tumours of the Nervous System. IARC Press (International Agency for Research on Cancer), Lyon, France 2000, pp 29–39Google Scholar