RESUMEN
PURPOSE: 5- fluorouracil (5-FU)-based chemotherapy with concomitant pelvic radiotherapy represents the gold standard of the adjuvant treatment of high-risk rectal cancer. This study aimed to determine the maximum tolerated dose (MTD) of weekly irinotecan (CPT-11) when combined with fixed 5FU/FA doses and pelvic irradiation. PATIENTS AND METHODS: Twenty- four patients with stage II or III rectal cancer were accrued. All had undergone curative surgery before entering the study. Standard pelvic radiotherapy was delivered (50.4 Gy, 1.8 Gy/ fraction in 5.5 weeks). The 5-FU/FA doses were 350/250 (mg/m(2)) in the first 6 patients and 250/100 in the remaining patients. Weekly doses of CPT-11 started at 30 mg/m(2) with escalation steps of 10 mg/m(2). CPT-11 was escalated when 3 patients had been monitored for 8 weeks, without a dose limiting toxicity (DLT). RESULTS: Twenty-three out of 24 patients completed the chemoradiation course. Only 1 patient discontinued the treatment due to persistent grade 3 diarrhea. Of the 144 planned weekly chemotherapy cycles, only 7 were omitted as a result of persisting grade 2-3 gastrointestinal toxicity in 3 patients and grade 3 neutropenia in 1 patient. Grade 3 gastrointestinal DLTs were observed at doses at the level of 30/250/100 in 1 patient and 70/250/100 in 2 patients. Late DLTs were severe radiation dermatitis and colitis at 40/ 350/250 (1 patient) and 70/250/100 (2 patients), respectively. With a follow-up of 18 months 20 (83.3%) patients remain disease- free. CONCLUSION: The administration of weekly CPT-11/ 5FU/FA with concomitant pelvic radiotherapy is feasible and effective. This treatment schedule is associated with mild myelosuppression and mild to moderate gastrointestinal toxicity. Caution should be paid on late radiotherapy-induced toxicities. The MTD of weekly CPT-11 is 30 mg/m(2) when combined with 5FU/FA doses (mg/m(2)) of 350sol;250 and reaches 60 mgsol;m(2) with lower doses of 5FU/FA (250/100).
RESUMEN
PURPOSE: The aim of this phase I trial was to deter- mine the maximum tolerated dose (MTD) of adjuvant che- motherapy (CT) with oxaliplatin in combination with capecitabine during concomitant pelvic radiotherapy (RT) in patients with rectal cancer. PATIENTS AND METHODS: Eligible patients had pathological stage II (T3-4N0M0) or III (any T N1-2M0) rectal adenocarcinoma, and no prior treatment other than curative resection. Fixed capecitabine dose (825 mg/m(2) bid on days 1-14 and 22-35) was given and external beam RT was delivered to the pelvis (50.4 Gy in 27 fractions in 5.5 weeks, with field reduction after 45 Gy in linear accelerator, 18Mev). Oxaliplatin was tested at 4 dose levels: 100, 110, 120 and 130 mg/m(2). The dose of oxaliplatin was escalated when all 3 entered patients at each level had been monitored for at least 8 weeks after the CT/RT course without dose limiting toxicities (DLTs). In the presence of a DLT at any dose level, a further 3 patients were enrolled. If only 1 of the 6 patients experienced a DLT, escalation could proceed. The MTD was defined as the level at which >/= 2 of 3 to 6 patients experienced DLTs. Fifteen patients (10 males and 5 females, median age 62 years) were enrolled at oxaliplatin dose levels of 100 (n=3), 110 (n=3), 120 (n=3) and 130 mg/m(2) (n=6). RESULTS: All patients completed the planned CT/RT course. Dose reduction or delay of the 2nd CT cycle was not required. No DLTs were observed at all dose levels. Overall, gastrointestinal and neurological toxicities were mild and transient. Toxicities included non-dose-limiting nausea / vomiting, diarrhea, dysesthesias in 2 level III and in 1 level IV patients. Grade II myelotoxicity, mainly neutropenia, was seen in 6 patients. With a median follow-up of 4 months (range 2-12) after the completion of CT/RT, late toxicities were restricted to grade II radiation colitis and dermatitis in 2 and 2 patients, respectively. CONCLUSION: The combination of pelvic RT, capecitabine and 3-weekly oxaliplatin is feasible and well tolerated. The MTD was not reached up to the dose of 130 mg/m(2) of oxaliplatin, which is the recommended dose.
RESUMEN
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.