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Purpose: To compare the results of empiric first-line therapy with paclitaxel/carboplatin/etoposide (PCE) versus gemcitabine/irinotecan, both followed by single-agent gefitinib, in patients with carcinoma of unknown primary site.Patients and Methods: Patients with previously untreated carcinoma of unknown primary site were randomized to receive either PCE or gemcitabine/irinotecan. Responding and stable patients continued treatment for 4 to 6 cycles. Patients with no evidence of tumor progression at that time received single-agent gefitinib until tumor progression. The trial was designed to detect an improvement in the 2-year survival rate from 20% to 30%.Results: Between September 2003 and July 2008, 198 patients entered this multicenter, community-based trial. Because of slow accrual, the trial was stopped short of its target accrual of 320 patients. Clinical characteristics were comparable for patients receiving PCE (N = 93) and gemcitabine/irinotecan (N = 105). PCE and gemcitabine/irinotecan produced similar 2-year survival (15% vs. 18%), median survival (7.4 months vs. 8.5 months), median progression-free survival (3.3 months vs. 5.3 months), and response rate (18% vs. 18%). Grade 3/4 neutropenia, thrombocytopenia, anemia, febrile neutropenia, and red blood cells transfusions were more common with PCE; diarrhea was more common with gemcitabine/irinotecan. The median duration of gefitinib maintenance was 3 months, suggesting no role as a maintenance therapy in this setting.Discussion: The PCE and gemcitabine/irinotecan regimens have comparable efficacy in the first-line treatment of patients with carcinoma of unknown primary site. Gemcitabine/irinotecan is the preferable regimen, due to its favorable toxicity profile. However, the moderate efficacy of both regimens underscores the need for novel treatment approaches in this patient population. [ABSTRACT FROM AUTHOR]

PURPOSE: To compare the combination of paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and topotecan (Hycamtin; Glaxo SmithKline, Philadelphia, http://www.gsk.com) with paclitaxel, carboplatin (Paraplatin; Bristol-Myers Squibb), and etoposide (Etopophos, VePesid; Bristol-Myers Squibb) in patients with previously untreated extensive-stage small cell lung cancer. PATIENTS AND METHODS: In this phase II trial, 120 patients were randomly allocated to receive either topotecan (1.5 mg/m(2) i.v. days 1, 2, and 3) and paclitaxel (175 mg/m(2) i.v. day 1) every 21 days orpaclitaxe l (200 mg/m(2) i.v. day 1), carboplatin (area under the concentration-time curve 6 i.v. day 1), and etoposide (50 mg/100 mg alternating daily by mouth days 1-10) every 21 days, each regimen for a maximum of eight cycles. The primary end points were objective response rate and time to progression. RESULTS: The paclitaxel-carboplatin-etoposide combination produced a significantly higher overall response rate (78% versus 48%), longer median time to progression (7.6 months versus 5.5 months), and greater number of patients free from progression at 1 year (14% versus 8%) compared with paclitaxel plus topotecan. There was no difference in overall survival. Toxicities were similar in the two treatment arms. CONCLUSIONS: The paclitaxel-carboplatin-etoposide combination produced a superior overall response rate and time to progression in patients with extensive-stage small cell lung cancer compared with paclitaxel plus topotecan. The platinum compounds continue to be a necessary component of the initial therapy for these patients. [ABSTRACT FROM AUTHOR]

Substantial advances have been made in this area, including improved diagnostic methods and better therapy regimens. The overall prognosis is not bright, but once treatable subsets of the population are recognized, these patients can have more hope than ever before. [ABSTRACT FROM AUTHOR]

PURPOSE: To evaluate the feasibility, toxicity, and efficacy of adding vinorelbine to the paclitaxel/carboplatin combination in the treatment of advanced non-small cell lung cancer. PATIENTS AND METHODS: Patients with advanced (stage IIIB/IV) non-small cell lung cancer who had received no previous chemotherapy were treated with the following three-drug regimen: paclitaxel, 200 mg/m2, 1-hour i.v. infusion, day 1; carboplatin, AUC 6.0 i.v., day 1; and vinorelbine, 22.5 mg/m2 i.v. days 1 and either 8 or 15. Treatment was repeated every 21 days. This phase II trial was conducted in a multicenter, community-based setting. RESULTS: Eighty-nine patients were treated with a median of four courses of therapy (range, one to eight). Thirty-one patients (35%) had major responses (two complete, 29 partial), and 36 patients (40%) had a minor response or stable disease. Actuarial median survival was 8.6 months; 1 year survival was 43%. Leukopenia was the major toxicity: 73% of patients had grade 3/4 toxicity, and 32 patients (36%) were hospitalized for neutropenia/fever (11% of total courses administered). Treatment-related death due to infection occurred in four patients (4%). CONCLUSIONS: This three-drug regimen is feasible and efficacious in the treatment of advanced non-small cell lung cancer. The addition of vinorelbine increases the incidence of severe leukopenia substantially when compared with the paclitaxel/carboplatin regimen. However, other toxicities are not markedly increased. Ongoing randomized trials will define the role of this regimen in the treatment of non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to determine the long-term follow-up on survival of patients with carcinoma of unknown primary site treated with taxane-based chemotherapy in a multicenter community-based setting. Patients and Methods: Patients were treated with three sequential phase II trials between 1995 and 1998 as follows: Study I: paclitaxel 200 mg/m2 intravenously (i.v.) Day 1, carboplatin AUC = 6 i.v. Day 1, and oral etoposide 50 mg daily alternating with 100 mg daily days 1-10 every 3 weeks; Study II: docetaxel 75 mg/m2 i.v. Day 1, cisplatin 75 mg/m2 i.v. Day 1, repeated every 3 weeks; Study III: docetaxel 65 mg/m2 i.v. Day 1, carboplatin AUC 6 i.v. Day 1, repeated every 3 weeks. A total of 144 patients (71 on Study I, 26 on Study II, 47 on Study III) were treated (45% had well differentiated carcinoma, 48% had poorly differentiated carcinomas, and 6% poorly differentiated neuroendocrine tumors). The majority of the patients had multiple sites of metastatic disease. Results: Thirty-six percent of all evaluable patients responded to therapy (27% partial and 9% complete responses). The median survival was 10 months with 1-, 2-, 3-, and 4-year survivals of 42%, 22%, 17%, and 17%, respectively. Follow-up ranges from 11 to 50 months. Women survived significantly longer than men. Thirty-one patients remain alive and 14 are progression-free. The primary toxicity was leukopenia with the carboplatin regimens and nausea and vomiting with the cisplatin regimen. A review of the survival of several large previously reported series of patients was compared to results after taxane-based chemotherapy. A compelling argument is made that chemotherapy is superior to best supportive care alone and that taxane-based chemotherapy is superior to other forms of chemotherapy. However, prospective randomized trials will be necessary to definitively demonstrate the superiority of this treatment compared to other therapies for these patients. Conclusion: Taxane-based chemotherapy for patients with carcinoma of unknown primary site appears to be clinically beneficial and is associated with long-term survival for a minority of patients at 2-, 3-, and 4-year follow-up. [ABSTRACT FROM AUTHOR]

PURPOSE: To evaluate the feasibility, toxicity, and therapeutic efficacy of 1-hour paclitaxel, carboplatin, continuous low-dose infusional 5-fluorouracil, and concurrent radiation therapy administered preoperatively in patients with localized esophageal cancer. PATIENT AND METHODS: Forty-nine patients with localized esophageal cancer, of either squamous cell 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/m2, 1 hour IV on days 1 and 22; carboplatin, AUC 6.0, IV on days 1 and 22; 5-fluorouracil, 225 mg/m2/day, continuous IV infusion on days 1 to 42; and radiation therapy, 45 Gy, administered by 1.8-Gy daily fractions beginning on day 1 of chemotherapy. Upon completion of this neoadjuvant regimen, patients were reevaluated, and all responding patients were resected within 6 weeks of completing neoadjuvant treatment. RESULTS: Administration of this combined modality regimen was associated with moderate toxicity and was tolerated by most patients. Leukopenia (65%) and esophagitis (31%) were the most common toxicities. Most patients did not require nutritional support. There were no treatment-related deaths during neoadjuvant 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 additional 11 patients (30%) having only microscopic residual disease. CONCLUSIONS: This novel, combined-modality neoadjuvant approach for the treatment of localized esophageal carcinoma is feasible and can be administered with toxicity that compares favorably to previously reported neoadjuvant regimens containing high-dose cisplatin. Preliminary assessment of efficacy is also encouraging, with 46% of patients having pathologic complete response. Further follow-up and larger numbers of patients are required to assess efficacy more definitively. [ABSTRACT FROM AUTHOR]