Preoperative combined modality therapy with paclitaxel, carboplatin, prolonged infusion 5-fluorouracil, and radiation therapy in localized esophagealcancer: Preliminary results of a Minnie Pearl Cancer Research Network Phase II Trial

PURPOSE To evaluate the feasibility, toxicity, and therapeutic efficacy of 1-hour p aclitaxel, carboplatin, continuous low-dose infusional 5-fluorouracil, and concurrent radiation therapy administered preoperatively in patients with l ocalized esophageal cancer. PATIENT AND METHODS Forty-nine patients with localized esophageal cancer, of either squamous ce ll carcinoma or adenocarcinoma histology, were enrolled into this phase II trial. All patients were candidates for surgical resection and received the following neoadjuvant therapy: paclitaxel, 200 mg/m(2), 1 hour IV on days 1 and 22; carboplatin, AUC 6.0, IV on days 1 and 22; 5-fluorouracil, 225 mg /m(2)/day, continuous IV infusion on days 1 to 42; and radiation therapy, 4 5 Gy, administered by 1.8-Gy daily fractions beginning on day 1 of chemothe rapy. Upon completion of this neoadjuvant regimen, patients were reevaluate d, and all responding patients were resected within 6 weeks of completing n eoadjuvant treatment. RESULTS Administration of this combined modality regimen was associated with modera te toxicity and was tolerated by most patients. Leukopenia (65%) and esopha gitis (31%) were the most common toxicities. Most patients did not require nutritional support. There were no treatment-related deaths during neoadjuv ant therapy; however, three patients (9%) experienced postoperative death. Preliminary assessment of treatment efficacy is encouraging, with 17 of 37 evaluable patients (46%) achieving pathologic complete remission and an add itional II patients (30%) having only microscopic residual disease. CONCLUSIONS This novel, combined-modality neoadjuvant approach for the treatment of loc alized esophageal carcinoma is feasible and can be administered with toxici ty that compares favorably to previously reported neoadjuvant regimens cont aining high-dose cisplatin. Preliminary assessment of efficacy is also enco uraging, with 46% of patients having pathologic complete response. Further follow-up and larger numbers of patients are required to assess efficacy mo re definitively.