Phase II Trial of Temozolomide in Patients with Relapsed Sensitive or Refractory Small Cell Lung Cancer, with Assessment of Methyl-Guanine-DNA Methyltransferase as a Potential Biomarker
Mené sur 64 patients atteints d'un cancer récidivant du poumon à petites cellules, cet essai de phase II évalue l'efficacité du témozolomide, notamment pour la prévention des métastases cérébrales, et identifie un biomarqueur potentiel de la réponse thérapeutique, la méthylation du gène MGMT
Purpose: This phase II study was conducted to assess the efficacy of temozolomide in patients with relapsed small cell lung cancer (SCLC). Experimental Design: Patients with disease progression after one or two prior chemotherapy regimens received temozolomide at 75mg/m2/day for 21 days of a 28-day cycle. The primary endpoint was overall response rate (ORR; complete plus partial response), which was evaluated separately in sensitive and refractory cohorts. In available tissue, we assessed MGMT promoter methylation status by PCR and MGMT expression by immunohistochemistry. Results: Sixty-four patients were accrued: 48 patients in the sensitive cohort and 16 in the refractory group. One complete response (CR) and 10 partial responses (PR) were noted in sensitive patients, ORR 23% [95% CI, 12% to 37%]. Two PRs were seen in the refractory cohort, ORR 13% [95% CI, 2% to 38%]. As second- and third-line treatment, the ORR was 22% [95% CI, 9% to 40%] and 19% [95% CI, 7% to 36%], respectively. Among patients with target brain lesions, 38% had a CR or PR [95% CI, 14% to 68%]. Grade ≥3 thrombocytopenia and neutropenia were observed in 9 patients (14%). A greater number of cases with methylated MGMT had a response compared to those with unmethylated MGMT (38% vs. 7%), p = 0.08. Conclusions: Temozolomide has activity in relapsed SCLC, particularly for brain metastases. Response to temozolomide may correlate with MGMT methylation in SCLC.