Preoperative chemotherapy and radiation for advanced esophageal carcinoma: comparison between once a day radiation and hyperfractionation, a single-institution experience.

The purpose of this study was to determine the toxicity and efficacy of single daily fractionation as compared with twice-a-day radiation therapy in combination with chemotherapy for preoperative locally advanced thoracic esophageal carcinoma. A retrospective survey was done of 42 patients undergoing concurrent chemotherapy and radiation for preoperative locally advanced thoracic esophageal carcinoma. Twenty-five patients had 5-fluorouracil ([5-FU]), 1,000 mg/m2/d by continuous infusion, days 1-5, and days 22-26), cisplatin (100 mg/m2 intravenously, days 2 and 22), and radiation to a total dose of 4,500 to 5,040 cGy in 180 cGy/fraction every day. Seventeen patients received 5-FU (300 mg/m2/d by continuous infusion, days 1 and 21), cisplatin (20 mg/m2/d for 1 hour, days 1-5 and days 17-20), vinblastine (1 mg/m2 intravenously, days 1-5 and days 17-21) and accelerated hyperfractionated radiation 150 cGy twice a day to a total dose of 4,500 cGy. Response rate, survival, local regional failure rates, and treatment toxicity of the two groups were compared. Surgery was aborted in one patient and another patient refused surgery in the single daily-fractionation group. All patients underwent surgery in the twice-daily group. Complete response (CR) was noted in 12 patients (52%) in the single daily-fractionation group as compared with 9 patients (52%) in the twice-daily group. The median and 3-year survival were 20 months and 35%, respectively, in the single daily-fractionation group. Corresponding figures were 18 months and 32%, respectively, in the twice-daily group. For the 2 groups combined, a statistically significant improvement in survival was observed among blacks who achieved a CR (31 months) as compared with the ones with residual disease (13.5 months). Local and regional failures were 28% and 17%, respectively, for the single daily-fractionation and twice-daily groups. Distant metastases remained significant in both groups and were 36% (single daily-fractionation) and 41% (twice-daily), respectively. Grades III to IV esophagitis and hematologic toxicity developed in 36% and 64% of patients of the single daily-fractionation and twice-daily groups, respectively. The incidence of late complications was 16% (single daily-fractionation) and 11.7% (twice-daily). Preoperative chemotherapy and radiation is effective to achieve a high pathologic CR. Both radiation therapy fractionation schedules are comparable in efficacy and toxicity. Further investigations should be done to assess whether ethnicity may play a role in the prognosis of esophageal carcinoma.

Efficacy of combined radiation, paclitaxel and carboplatin for locally advanced non-small cell lung carcinoma.

Locally advanced non-small cell lung carcinoma (NSCLC) has a poor prognosis when treated with conventional chemotherapy and radiation. New chemotherapy agents like paclitaxel may increase the sensitivity of tumors cells to radiation and potentially improve the outcome. The optimal combination of taxane-based chemotherapy agents and radiation is still unclear. We investigated the feasibility of induction chemotherapy followed by concurrent near systemic dose of chemotherapy with radiation. A prospective survey of 29 previously untreated patients with unresectable stage III (15 IIIA, 14 IIIB) NSCLC treated with paclitaxel and carboplatin in combination with radiation was reviewed. The patients received 2 cycles of paclitaxel 225 mg/m2 intravenously (i.v.) over 3 hours, days 1, 22; carboplatin at area under the curve (AUC) 6 based on Calvert formula days 1, 22 following completion of the paclitaxel infusion. Following induction chemotherapy, radiation therapy started on day 43 until completion to a tumor dose of at least 5960 cGy. Cycles 3 and 4 of chemotherapy were begun on days 43 and 63, respectively, and consisted of paclitaxel 175 mg/m2 i.v. over 3 hours, and carboplatin at AUC 6 following paclitaxel infusion. The response rate, acute toxicity, long-term complications, pattern of failure and survival were evaluated and compared to previous studies in the literature. Two patients were lost to follow-up. The response rate to induction carboplatin/paclitaxel was 52%. An overall response rate (complete and partial responders) of 85% was obtained following chemotherapy and radiation. Grade 3-4 acute side-effects were recorded in 9 patients (31%) and consisted of esophagitis (8 patients) and anemia (1 patient). One patient died from cachexia 3 months following treatment (3.7%). The median survival and 3-year survival were 15 months and 30%, respectively, for the remaining 27 patients at a median follow-up of 11 months. There was no difference in survival between stages IIIA and IIIB at 2 years (IIIA: 22%, IIIB: 31%). Local or regional recurrences and distant metastases developed in 9 patients (33%) and 13 patients (46%), respectively. The combination of paclitaxel, carboplatin and radiation for locally advanced non-small cell carcinoma is feasible with acceptable toxicity. The response rate compares favorably with previously reported studies. The decrease of tumor volume following induction chemotherapy allows sparing of the lungs from the toxicity of radiation. However, grades 3-4 esophagitis remain significant. The addition of amifostine may be beneficial in this setting.