Long-term survival of patients with glioblastoma treated with radiotherapy and lomustine plus temozolomide.

Abstract

PURPOSE:

To evaluate long-term survival in a prospective series of patients newly diagnosed with glioblastoma and treated with a combination of lomustine (CCNU), temozolomide (TMZ), and radiotherapy.

PATIENTS AND METHODS:

Thirty-nine patients received radiotherapy of the tumor site only (60 Gy) and CCNU/TMZ chemotherapy (n = 31 received standard-dose CCNU, 100 mg/m2 on day 1 and TMZ 100 mg/m(2)/d on days 2 to 6; n = 8 received intensified-dose CCNU 110 mg/m(2) on day 1 and TMZ 150 mg/m(2) on days 2 to 6) for up to six courses.

RESULTS:

In the whole cohort, the median overall survival (mOS) was 23.1 months; 47.4% survived for 2 years, and 18.5% survived for 4 years. After a median follow-up of 41.5 months, mOS had not been reached in the intensified group and was significantly higher than in the standard group (22.6 months; P = .024). In the intensified group, four of eight patients survived for at least 56 months, two of them without recurrence. O(6)-methylguanine-DNA methyltransferase (MGMT) gene promotor methylation in the tumor tissue was associated with significantly longer mOS (methylated, 34.3 months v nonmethylated, 12.5 months). A multivariate Cox proportional hazard model revealed MGMT status (methylated v nonmethylated; relative risk [RR] of death, 0.43; P = .003) and chemotherapy dose (intensified v standard; RR, 0.37; P = .012) as independent prognostic factors. WHO grade 4 hematoxicity was observed more frequently in the intensified group (57% v 16%).

CONCLUSION:

The combination of radiotherapy, CCNU, and TMZ yielded promising long-term survival data in patients with newly diagnosed glioblastoma. Intensification of CCNU/TMZ chemotherapy may add an additional survival benefit, albeit with greater acute toxicity.

• Authors: Martin Glas, Caroline Happold, Johannes Rieger, Dorothee Wiewrodt, Oliver Bähr, Joachim P Steinbach, Wolfgang Wick, Rolf-Dieter Kortmann, Guido Reifenberger, Michael Weller, Ulrich Herrlinger
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 8 Pg. 1257-61 (Mar 10 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19188676 (Publication Type: Journal Article)

Chemical References

• Lomustine
• Dacarbazine
• Temozolomide

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Combined Modality Therapy
• Dacarbazine (administration & dosage, analogs & derivatives)
• Female
• Glioblastoma (mortality, therapy)
• Humans
• Lomustine (administration & dosage)
• Male
• Middle Aged
• Proportional Hazards Models
• Prospective Studies
• Temozolomide