Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases.

PURPOSE: To determine the efficacy, tolerability, and safety of concurrent temozolomide and radiotherapy in patients with previously untreated brain metastases. PATIENTS AND METHODS: Fifty-two patients with brain metastases from solid tumors were randomized to oral temozolomide (75 mg/m(2)/d) concurrent with 40-Gy fractionated conventional external-beam radiotherapy (2 Gy, 5 d/wk) for 4 weeks versus 40-Gy radiotherapy alone. The group receiving temozolomide and radiotherapy continued temozolomide therapy (200 mg/m(2)/d) for 5 days every 28 days for an additional six cycles. The primary end points were radiologic response and neurologic symptom evaluation. RESULTS: The objective response rate was significantly (P =.017) improved in patients receiving temozolomide and radiotherapy versus radiotherapy alone. Among 24 patients assessable for response in the temozolomide group, 23 (96%) of 24 responded, including nine (38%) patients with a complete response and 14 (58%) patients with a partial response. With radiotherapy alone, 14 (67%) of 21 assessable patients responded, including seven (33%) complete responses and seven (33%) partial responses. There was marked neurologic improvement in the group receiving temozolomide, and the proportion of patients requiring corticosteroids 2 months after treatment was lower in the temozolomide group compared with radiotherapy alone (67% v 91%, respectively). Daily temozolomide concurrent with radiotherapy was generally well tolerated; however, grade >or= 2 nausea (48% v 13%, P =.13) and vomiting (32% v 0%, P =.004) were significantly increased in the temozolomide group. Hematologic toxicity was predictable and reversible. CONCLUSION: Temozolomide is safe, and a significant improvement in response rate was observed when administered in combination with radiotherapy in patients with previously untreated brain metastases. A larger randomized trial is warranted to verify these results.

Randomized phase III trial of radiation treatment +/- amifostine in patients with advanced-stage lung cancer.

PURPOSE: This multicenter trial investigated whether daily pretreatment with amifostine (A) could reduce the incidence of acute and late lung toxicity and esophagitis without affecting antitumor efficacy of radiation in advanced lung cancer. PATIENTS AND METHODS: Radiotherapy (XRT) patients (n = 146) received a daily fraction of 2 Gy/5 days/week to a total of 55-60 Gy +/- amifostine 340 mg/m(2) administered daily 15 min before irradiation. Acute and late toxicities were graded from 0 to 4 according to the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer system. RESULTS: Ninety-seven patients were evaluated 2 months post-XRT for the incidence of pneumonitis; 43% (23/53) of patients in the XRT arm and 9% (4/44) in the A + XRT arm experienced > or = Grade 2 pneumonitis (p < 0.001) [corrected]. Forty-nine percent (26/53) of patients in the XRT arm and 16% (7/44) in the A+XRT arm demonstrated changes representative of > or = Grade 2 lung damage (p < 0.001). At 6 months, fibrosis was present in 53% (19/36) receiving XRT vs. 28% (9/32) receiving A+XRT (p < 0.05). Incidence of esophagitis > or = Grade 2 during Week 4 was 42% (31/73) in the XRT arm vs. 4% (3/73) in the A+XRT arm (p < 0.001). Among 97 patients evaluable for response 2 months after XRT, complete or partial response was present in 76% (40/53) of patients in the XRT arm and 75% (33/44) in the A+XRT arm (p = 1.0). CONCLUSION: Amifostine reduces the incidence of pneumonitis, lung fibrosis, and esophagitis in radiotherapy patients with lung cancer without compromising antitumor efficacy.