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.

Comparison of effectiveness between chemotherapy alone versus chemo-radiotherapy in stage III non-small cell lung cancer.

Combined chemotherapy with radiotherapy has been claimed to be superior to radiotherapy alone in stage III non-small cell lung cancer (NSCLC). The present study was designed to give chemo-radiotherapy with 300 cGy only on the day the cytotoxic drugs are administered. The aim was to exploit the cell cycle synergism between the two treatments. Forty-five patients of stage IIIA+B with inoperable NSCLC were randomized in two groups. Group A to be treated with chemotherapy only and group B to be treated with chemotherapy plus radiotherapy. Drugs for group A were: cisplatinum 90 mg/m(2), vindesine 3 mg/m(2) and epirubicin 40 mg/m(2) once every 3 weeks for 8 courses. Group B: cisplatinum 60 mg/m(2), vindesine 3 mg/m(2) and epirubicin 30 mg/m(2) plus 300 cGy radiation, every two weeks for 8 cycles. Then, estimation of response was done. Toxicity was tolerable. In group A the response rate was 52%, in group B 90% (partial and complete). The difference was statistically significant. Additional radiotherapy up to 5,400 cGy was given in patients of group B while patients of group A had palliative radiation on recurrence. Survival rate was significantly longer for patients of group B.

Measurement of the restricted linear energy transfer of stray radiation close to the treatment volume of 12 and 18 MeV clinical photon beams.

The restricted dose mean linear energy transfer (LET) (L500,D) of the stray radiation field a few centimeters outside the treatment volume has been measured for 12 and 18 MV photons produced by a clinical Therac-20 (AECL) accelerator. The measurements were performed as a function of field size and distance from the edge of the treatment volume, using the method of the high-pressure ionization chamber. Contrary to what was found in a previous investigation for a clinical Co-60 unit and despite the presence of photoneutrons (in the case of 18 MV photons), the L500,D outside the beam does not increase significantly relative to the L500,D of the primary beam.

Measurement of the restricted dose mean LET outside the primary beam of a 60Co radiotherapy unit.

A recently developed method for the direct measurement of the restricted dose mean LET (cutoff energy = 500 eV) of an unspecified photon or electron radiation field with the high-pressure ionization chamber has been utilized to investigate the variation of this radiobiologically important parameter outside the primary beam of a clinical 60Co unit. A small high-pressure tissue-equivalent ionization chamber was used, and its characteristics and experimental considerations for the present investigation are reported. Measurement of the restricted dose mean LET at the examined points outside the primary 60Co beam showed an increase of 50% with respect to the restricted dose mean LET of the uncollimated 60Co beam. No significant variation was noted with off-central axis distance, field size, wedge filter, or depth below Perspex slabs. Dose rates at the points of measurement outside the primary 60Co beam were 1-5% of the dose rate in the primary beam.