Effective radiochemotherapy with cisplatin and etoposide for the management of patients with locally inoperable and metastatic esophageal carcinoma.

Background: The limited therapeutic value of available chemotherapeutic drug combinations in patients with advanced esophageal carcinoma, the documented synergistic activity of etoposide and cisplatin, which might be further enhanced by simultaneous radiotherapy, and promising though only preliminary therapeutic results with this combination regimen have stimulated the present Phase II trial. The specific aim of the study was to determine the efficacy and tolerance of this combined treatment approach in previously untreated patients with either local regional unresectable or metastatic esophageal carcinoma.

Methods: Thirty patients with Stage IIIB or IV squamous cell or adenocarcinoma of the esophagus were entered in this study between October 1992 and November 1994. Chemotherapy was comprised of cisplatin, 30 mg/m2, combined with etoposide, 120 mg/m2, both given intravenously on 4 consecutive days. Treatment courses were repeated every 4 weeks. Radiation therapy (total dose, 5000 centigray) was administered concurrently during the 2nd and 3rd chemotherapy course, during which both drugs were given with a 25% dose reduction.

Results: After a median of 4 chemotherapeutic treatment courses (range, 1 to 6 courses), 3 patients had a complete response for 5, 8, and 11.5 months, and 9 patients had a partial response lasting for a median duration of 5.3 months (range, 2.5 to 7.5 months), yielding an overall response rate of 40% (95% confidence interval, 23-59%). The response rates tended to be higher for squamous cell carcinomas (11 of 23; 48%) than for adenocarcinomas (1 of 7), as well as for locoregional disease (7 of 13; 54%) than for patients with disseminated disease (5 of 17; 29%). For the entire study population, median time to progression was 5.4 months (range, 1.5 to 13.5 months), and median survival was 9.2 months (range, 1.5 to 28 months), with 4 patients still alive at the time of this report. Clinically, the most important toxic effect was myelosuppression. Grade 3-4 granulocytopenia occurred in 16 patients (53%), severe thrombocytopenia in 11 (37%), and Grade 3 anemia in 5 (17%). There were four hospitalizations among three patients for the management of fever during neutropenia. Other nonhematologic side effects were generally mild or modest, and most commonly included nausea/emesis (40%), mucositis and/or esophagitis during simultaneous radiotherapy (40%), and alopecia (43%).

Conclusions: Combined radiochemotherapy with cisplatin and etoposide is active against advanced esophageal carcinoma, but can be associated with significant hematotoxicity. Although the therapeutic potential of this regimen appears to be comparable to other, conventional fluorouracil/cisplatin-based chemotherapy, less toxic and more effective regimens need to be identified.