Combined paclitaxel, cisplatin, and etoposide for patients with previously untreated esophageal and gastroesophageal carcinomas.

BACKGROUND: Paclitaxel (T), etoposide (E), and cisplatin (P) are each active in gastric carcinoma, either as single agents or as part of a multidrug regimen. To the authors' knowledge, the combination of these three agents in the treatment of patients with esophageal or gastroesophageal carcinoma has not been previously studied. METHODS: Previously untreated patients with locally advanced carcinoma of the stomach, esophagus, or gastroesophageal (GE) junction received at least 2 cycles of TPE administered twice weekly for 3 weeks, with the cycle repeated every 28 days. Drug doses, administered over 3 hours on either Monday and Thursday or Tuesday and Friday, consisted of T 50 mg/m2/dose, P 15 mg/m2/dose, and E 40 mg/m2/dose. For patients with local disease only, subsequent therapy consisted of radiation with or without surgical resection. RESULTS: Twenty-five patients with gastric (10) or gastroesophageal or GE junction (15) carcinoma were treated. Eighteen had locally advanced disease and 7 had liver metastases at presentation. Hematologic toxicity, namely, Grade 3 anemia and neutropenia, was experienced by all patients. The median number of treatment cycles was 4 (range, 2-6). Three patients were not evaluable for response. All 22 evaluable patients responded; 3 were complete responders and 19 were partial responders. Eleven patients received radiation therapy with (6) or without (5) concomitant 5-fluorouracil, and 8 patients subsequently underwent surgical resection. Three of 8 patients had no tumor at surgery, 4 had minimal microscopic tumor at the primary site, and 3 had microscopic lymph node involvement. Twenty-three patients are alive, of whom 14 are without evidence of disease. Two patients with metastatic disease at presentation died at 9 and 29 months, respectively. The median survival was 12.5 months (range, 6 to 30+ months). CONCLUSIONS: Multifractionated TPE chemotherapy is a highly active regimen in gastric and gastroesophageal carcinoma. It could be evaluated in Phase III trials against other active regimens for the treatment of patients with this disease. The introduction of 5-fluorouracil could also be an interesting direction to explore because of its primary role in the treatment of patients with gastric and esophageal carcinoma.

Paclitaxel, cisplatin, etoposide combination chemotherapy: a multifractionated bolus dose schedule for non-small cell lung cancer.

In this phase II study, paclitaxel was added to the combination of cisplatin and etoposide (TPE regimen), in 37 patients with advanced non-small cell lung cancer, using a multifractionated dosing schedule. The total dose of paclitaxel (175-200 mg/m2); cisplatin (75 mg/m2); and etoposide (175-200 mg/m2) was divided into five daily doses administered over 3 h with cycles repeated at 21-28 days. 15 patients had stage III A or B disease and 22 stage IV disease. 32 patients were evaluable for toxicity and 37 for response. Neutropenia was the most prominent toxicity. Grade 3 or grade 4 neutropenia was observed in 12 (38%) and 9 (25%) of the patients, respectively and 11 patients required hospitalisation. 3 patients died secondary to chemotherapy related sepsis. Diarrhoea (grade 3, 3 patients; grade 4, 2 patients) was the only other significant non-haematological acute toxicity. The optimal dose rate for this multifractionated regimen was paclitaxel 35 or 40 mg/m2/fraction; cisplatin 15 mg/m2/fraction; etoposide 35 or 40 mg/m2/fraction. Responses were observed in 28 of 37 evaluable patients (3 complete response; 25 partial responses [76%]. 22 patients are alive; 8 with stage III B disease received radiation or surgery (3 had minimal or no tumour in the pathology specimen). TPE is a highly active regimen for non-small cell lung cancer and multifractionated dose scheduling is a feasible and well tolerated system.

Neoadjuvant treatment of stage IIIA non-small cell lung cancer. Long-term results.

The multimodality approach to locally advanced Stage III non-small cell lung cancer is continuing to evolve. In this trial, 54 patients with surgically staged IIIA disease were treated with neoadjuvant chemotherapy, surgical resection, and chest radiotherapy. Response to four cycles of CAP chemotherapy (cyclophosphamide, doxorubicin, cisplatin) was 39% (8% complete responses). One septic death occurred. Thoracotomy was performed on 31 patients, of whom 29 (56%) were resected and 24 (44%) were completely resected. Complete resections were more frequently observed in chemotherapy responders. Extranodal mediastinal extension in nonresponding patients was the most frequent reason not to attempt thoracotomy. The overall median times to progression and survival were 11.6 (.7-66.5) and 17.9 (2.8-71.4) months. Long-term disease-free survival was observed in 11 patients (20%) with a median follow-up of 46.5 (24-71) months. All these patients underwent complete resection and constitute 46% of the patients undergoing complete resection. Median times to progression and survival were 33.4 (5.0-66.5) and 33.5 (10-71.4) months for completely resected patients. Although the ability to perform surgery identified a population that has favorable locoregional control and disease-free survival, distant relapse continues to represent the major obstacle to enhanced survival in resected patients. Unresected patients, however, are likely to relapse in both local and distant sites. Response to chemotherapy may not only enhance systemic control, but may also increase the probability of complete resection. Randomized trials should be conducted to evaluate the role of individual modalities (surgery, chemotherapy, or radiotherapy) while applying the remaining modalities maximally. The temptation to compare different treatment approaches should be resisted.

Hepatic metastatectomy for low-grade leiomyosarcoma: a case report.

A patient with multiple bilateral liver metastases from a gastrointestinal leiomyosarcoma underwent staged sequential metasta- tectomy and at 3 years is tumor-free.

Neoadjuvant chemotherapy in marginally resectable stage III M0 non-small cell lung cancer: long-term follow-up in 41 patients.

Forty-one patients with marginally resectable stage III M0 non-small cell lung cancer (NSCLC) were entered into a study evaluating neoadjuvant cyclophosphamide, adriamycin, and cisplatin chemotherapy (CAP) followed by radiotherapy and subsequent resection. Postoperative radiotherapy and additional CAP were also administered. The objective disease regression rate prior to surgery was 72% (2 complete, 12 partial, and 7 minimal responses). Thoracotomy was carried out in 37 patients (90%), with resection of all gross disease in 36 patients (97%). Relapse occurred in 22 (61%) of the resected patients, involving chest only (four patients), chest and extra thoracic (nine patients), and extra thoracic only (nine patients). Subsequent CNS relapse developed in 9 (25%) of 36 postop patients in association with other sites of relapse (five patients) or as a solitary location (four patients). Only one of seven patients receiving prophylactic cranial irradiation (PCI) developed CNS relapse compared with 7 (26%) of 27 patients not receiving PCI. The median long-term follow-up for 14 living patients is 53+ months, with a rang of 38+ to 71+ months. Median survival for all patients is 32 months, with 1-year survival being 75%. The survival curve shows a plateau of 31% from 3 to 5+ years. Using a log rank test, no prognostic subgroups could be identified that significantly affected response rate, disease-free survival, or overall survival. While neoadjuvant CAP followed by radiotherapy appears to improve survival, more effective chemotherapy along with randomized studies are needed to determine the role of initial chemotherapy in marginally resectable NSCLC.