Prognostic Factors for the Selection of Patients Eligible for Second-Line Chemotherapy in Advanced Biliary Tract Cancer.

BACKGROUND: The efficacy of second-line chemotherapy (CT2) after the failure of first-line chemotherapy (CT1) for advanced biliary tract cancer (BTC) has not been established. We investigated the favorable prognostic factors for CT2 to determine which patients could be expected to benefit from CT2. METHODS: From a total of 168 patients who were treated with chemotherapy at our institution between January 2003 and December 2012, we retrospectively reviewed 50 patients who received CT2. Patients were treated with various chemotherapeutic combinations as CT1 and CT2. RESULts: The median overall survival (OS) of patients who received and CT2 was 10.2 and 5.5 months, respectively. Good performance status (PS), a serum albumin level >3.5 g/dl and metastasis to only 1 organ were independent prognostic factors that affected the OS of the patients who received CT2. Patients who had only 1 metastastic organ, a good PS and a serum albumin level >3.5 g/dl at the beginning of CT2 demonstrated prolonged survival compared to patients who did not exhibit these 3 factors (9.5 vs. 4.3 months, p < 0.005). CONCLUSIONS: CT2 should be considered for patients with advanced BTC, especially for those who have only 1 metastatic organ and remain in generally good medical condition after the failure of CT1.

A phase I/II and pharmacogenomic study of pemetrexed and cisplatin in patients with unresectable, advanced gastric carcinoma.

This phase I/II study was conducted to determine the maximum recommended dose of pemetrexed when given in combination with a fixed dose of cisplatin, and the efficacy, toxicity and association of 5,10-methylenetetrahydrofolate reductase (MTHFR) variants with this pemetrexed--cisplatin combination, in patients with unresectable, advanced gastric carcinoma. Patients 18-70 years of age, with stage IV disease or post-surgery recurrence, no earlier palliative chemotherapy, 0 or 1 Eastern Cooperative Oncology Group performance status, were included. The cisplatin dose was 75 mg/m. In phase I, the initial dose of pemetrexed was 600 mg/m, escalated in 100 mg/m increments. In phase II, efficacy, including overall response rate, overall survival, as well as toxicity and MTHFR pharmacogenetics were investigated. Phase I enrolled 16 patients; 700 mg/m was defined as pemetrexed recommended dose. Thirteen serious adverse events were reported; the most common grade 3/4 toxicities were haematologic (10 of 13, 76.9%). Phase II enrolled 73 patients, 69 qualified for safety and 68 for efficacy analysis; 65 for pharmacogenomic analysis. Overall response rate was 23.5% (14.1%, 35.4%), disease control rate 55.9%, median overall survival 11.8 months (95% confidence interval, 7.2-18.5 months), progression-free survival 4.9 months (95% confidence interval, 2.8-7.1 months), and median response duration 5.4 months. Patients with MTHFR A1298C variants had median overall survival of 6.6 months, significantly shorter than patients with the wild type (median 18.5 months, P=0.001). The pemetrexed--cisplatin combination in patients with advanced gastric cancer generates modest efficacy and a manageable toxicity profile. The reduced overall survival in patients with MTHFR A1298C polymorphism variants deserves further investigation.

Capecitabine monotherapy as salvage treatment after failure of chemotherapy containing oxaliplatin and irinotecan in patients with metastatic colorectal cancer.

AIM: There has been limited data on capecitabine monotherapy in metastatic colorectal cancer (CRC) patients who were previously treated with both oxaliplatin/5-fluorouracil(FU)/leucovorin (FOLFOX) and irinotecan/5-FU/leucovorin (FOLFIRI). METHODS: We analyzed 20 patients between August 2002 and March 2008 with metastatic CRC who had been treated with capecitabine monotherapy after the failure of FOLFOX and FOLFIRI. RESULTS: Overall, one partial response was observed (overall response rate, 5%) and stable disease was observed in 11 patients (55.0%). The disease control rate was 60.0%. The median progression-free survival (PFS) was 2.3 months (95% CI 1.9-2.7) and the median overall survival (OS) was 5.3 months (95% CI 4.6-6.0). Patients without ascites had longer PFS than those with ascites (P=0.02). Patients with more than three metastatic sites had poorer OS than those with less than two (P=0.01). Grade 3 or 4 non-hematological toxicities included hand-foot syndrome in one patient. There were no grade 3 or 4 hematological toxicities or treatment-related deaths. CONCLUSION: The capecitabine monotherapy had a moderate disease control rate and a tolerable toxicity profile as third-line or fourth-line treatment for metastatic CRC patients who were refractory to standard chemotherapy with no further treatment options.

A Phase II study of paclitaxel by 24-hour infusion and ifosfamide in anthracycline-resistant metastatic breast carcinoma.

BACKGROUND: A Phase II study was performed to investigate the efficacy and tolerability of paclitaxel and ifosfamide chemotherapy for the treatment of anthracycline-resistant metastatic breast carcinoma (MBC). METHODS: Recurrent or progressed MBC within 12 months after anthracycline-based chemotherapy was defined as anthracycline-resistant. A 24-hour infusion of paclitaxel (175 mg/m(2)) on Day 1 and subsequent infusions of ifosfamide (1.8 g/m(2)/day) with mesna (360 mg/m(2)/day) on Days 2- 4, were performed every 3 weeks. Twenty-one patients were eligible for toxicity analysis. Response rate and survival duration were evaluated in 21 patients. Frontline chemotherapy was the FAC (5-fluorouracil, doxorubicin, cyclophosphamide) regimen in all patients. RESULTS: Objective response was found in 9 patients (42.9%), including complete response in 3 (13.4%). Median response duration and median survival duration were 10 months (range, 2-24+) and 19+ months (range, 2-32+), respectively. Sixteen (76%) experienced Grade 3/4 leukopenia controllable with granulocyte macrophage colony-stimulating factor. Other significant toxicities were peripheral neuropathy (n = 3), mucositis (n = 2), and liver dysfunction (n = 1). However, there was no chemotherapy-related death. CONCLUSIONS: Paclitaxel by 24-hour infusion combined with ifosfamide is efficacious in the treatment of anthracycline-resistant MBC with tolerable toxicity. Further trials verifying the result of the authors' study are warranted.

Phase II study of docetaxel and cisplatin combination chemotherapy in metastatic or unresectable localized non-small-cell lung cancer.

BACKGROUND: Docetaxel is highly active in the second-line treatment of patients with metastatic or unresectable locally advanced nonsmall-cell lung cancer (NSCLC). As there is a need for first-line chemotherapy that is more effective than standard platinum-based chemotherapy, this study was undertaken to evaluate the efficacy and tolerability of a docetaxel/cisplatin combination as first-line chemotherapy in advanced NSCLC. METHODS: Newly diagnosed, chemotherapy-naive patients with histologically confirmed NSCLC (measurable stage IIIB/IV NSCLC; Karnofsky performance status, 70-100; adequate bone marrow, renal, hepatic, and cardiac function) were eligible for the study. Docetaxel 75 mg/m2 was administered IV over 1 h, followed immediately by cisplatin 75 mg/m2, given IV over 30 min, with cycles repeated every 3 weeks, for up to six or nine cycles. RESULTS: Thirty-nine patients were enrolled and treated. Their median age was 59 years (range, 32-71 years) and median performance status, 90 (range, 70-100). Histologically, 23 patients (59%) had adenocarcinoma, 12 (30.8%) had squamous cell carcinoma, and 16 patients (41%) had stage IV disease. Thirty-seven patients were eligible for inclusion. In the 39 patients evaluable for safety, significant grade 3/4 toxicities included neutropenia (82%), nausea (10.3%), fatigue (10.3%), and diarrhea (7.7%). Of the 33 patients evaluable for response, 16 patients (48.5%) achieved a partial response and 7 showed progressive disease. Median overall survival time in all eligible patients was 10.5 months. CONCLUSION: Docetaxel/cisplatin produced promising response rates that compare favorably with those of current standard platinum combinations, with manageable toxicity. Further investigations of this first-line combination in NSCLC are warranted.