A phase II study of paclitaxel by weekly 1-h infusion for advanced or recurrent esophageal cancer in patients who had previously received platinum-based chemotherapy

Purpose

To evaluate the efficacy and safety of weekly paclitaxel (Taxol^®) in patients with advanced or recurrent esophageal cancer.

Methods

Fifty-three patients with recurrent or advanced esophageal cancer who had previously received platinum-based chemotherapy were treated with paclitaxel 100 mg/m² once weekly by 1-h infusion on days 1, 8, 15, 22, 29, and 36 of a 49-day cycle. Fifty-two patients were evaluable for efficacy and 53 for safety. Forty-one (77%) patients had recurrent, and 12 (23%) had advanced disease. Most patients (52/53) had squamous cell carcinoma, and one had adenocarcinoma.

Results

A median of 2 cycles was delivered (range 1–8). The overall response rate was 44.2% (23/52; 95% confidence interval (CI) 30.5, 58.7%), with 4 patients (7.7%) achieving complete response. The median duration of response was 4.8 months, and median overall survival was 10.4 months. The most common Grade 3 or 4 adverse events were neutropenia (52.8%), leukopenia (45.3%), anorexia (9.4%), and fatigue (9.4%). Adverse events resulted in treatment discontinuation in 34.0% of patients and dose reductions in 43.4%. There were no treatment-related deaths.

Conclusions

Weekly paclitaxel demonstrated efficacy and manageable toxicity in patients with advanced or recurrent esophageal cancer and may be a treatment option for this population.

     

Prognostic role of microRNA polymorphisms in patients with advanced esophageal squamous cell carcinoma receiving platinum-based chemotherapy

Purpose

MicroRNA (miRNA) polymorphisms contribute to cancer susceptibility and prognosis. The aim of this study was to evaluate the effects of miRNA polymorphisms on clinical outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) treated with platinum-based chemotherapy.

Methods

Five polymorphisms (miR-146a rs2910164, miR-196a2 rs11614913, miR-100 rs1834306, miR-125a rs12976445 and miR-26a1 rs7372209) were genotyped in 378 patients with advanced ESCC recruited at Zhongshan Hospital. The associations between genotypes and drug response, toxicity, and overall survival were analyzed.

Results

miR-146a rs2910164 was significantly associated with an increased risk of severe hematological toxicity [odds ratio = 0.374, 95 % confidence interval (CI) 0.171–0.819, P = 0.014]. The TT genotypes of both miR-196a2 rs11614913 and miR-125a rs12976445 were associated with worse survival [hazard ratio (HR) = 1.552, 95 % CI 1.112–2.165, P = 0.010; HR = 2.171, 95 % CI 1.173–4.017, P = 0.014, respectively]. Combined analysis revealed a 4.073-fold increased risk of death in patients carrying two unfavorable genotypes (P = 0.002).

Conclusions

Taken together, these findings indicate that miRNA polymorphisms may predict prognosis in advanced ESCC patients receiving platinum-based chemotherapy.     

Gemcitabine and docetaxel as second-line chemotherapy for patients with nonsmall cell lung carcinoma who fail prior paclitaxel plus platinum-based regimens.

BACKGROUND: Treatment options for patients with recurrent nonsmall cell lung carcinoma (NSCLC) remain limited as a result of poor activity of older agents after platinum-based therapy. In the current Phase II study, the authors evaluated the combination of gemcitabine and docetaxel in patients with recurrent NSCLC. METHODS: Patients with advanced NSCLC (Stage IIIB-IV), a World Health Organization performance status (PS) < or = 2, prior paclitaxel plus platinum-based chemotherapy, and unimpaired hematopoietic and organ function were eligible. Chemotherapy was administered as follows: gemcitabine 1000 mg/m(2) was administered on Days 1 and 8 followed by docetaxel 100 mg/m(2) on Day 8, and this regimen was recycled every 21 days. Prophylactic granulocyte-colony stimulating factor was administered on Days 10-14 or until the patient achieved a white blood cell count > or = 5000/microL. RESULTS: Of 43 patients who were entered on the study, 41 patients were evaluable for response, and all were evaluable for toxicity. The median patient age was 63 years (range, 47-70 years), the median PS was 1 (range, 0-2), there were 38 male patients, and there were 5 female patients. Four patients had Stage IIIA disease, 17 patients had Stage IIIB disease, and 22 patients had Stage IV disease. Histologies included 19 patients with adenocarcinoma, 18 patients with squamous cell carcinoma, and 3 patients with large cell carcinoma. Metastatic sites included lymph nodes in 28 patients, bone in 6 patients, liver in 5 patients, brain in 5 patients, lung nodules in 8 patients, adrenals in 7 patients, and other sites in 3 patients. All patients had received prior paclitaxel plus platinum-based treatment; 28 patients had received prior paclitaxel, ifosfamide, and cisplatin. Objective responses were partial response (PR) in 14 of 43 patients [33%; 95% confidence interval [95%CI], 18.5-46.6%], stable disease (SD) in 16 of 43 patients (37%; 95% CI, 22.8-51.6%), and progressive disease (PD) in 13 of 43 patients (30%; 95% CI, 16.3-43.7%). The median time to disease progression was 6 months (range, 1.0-20.0+ months), and the median survival was 8.5 months (range, 1.5-20.0+ months). The 1-year survival rate was 28%. Grade 3-4 neutropenia was experienced by 53% of patients (30% Grade 4), with 14% of patients experiencing febrile neutropenia. Grade 3 thrombocytopenia was experienced by 7% of patients (no Grade 4), whereas other Grade 3 nonhematologic toxicities were never encountered. CONCLUSIONS: The combination of gemcitabine and docetaxel is active and is well tolerated in patients with advanced NSCLC who have failed prior taxane plus platinum chemotherapy. This regimen represents a tolerable and effective combination to apply in the palliative treatment of patients with recurrent NSCLC.     

Gemcitabine and paclitaxel chemotherapy for advanced urothelial carcinoma in patients who have received prior cisplatin-based chemotherapy

Background  The objective of this study was to evaluate the efficacy and toxicity of combination chemotherapy with gemcitabine and paclitaxel as a second-line regimen in patients with advanced urothelial carcinoma. Methods  Twenty patients with advanced urothelial carcinoma who were resistant to an M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) chemotherapy regimen were administered chemotherapy consisting of intravenous gemcitabine 2500 mg/m² and paclitaxel 150 mg/m² (GP) every 2 or 3 weeks. Results  The patients received a median of 7.7 cycles of treatment (range, 2–20 cycles). Six of the 20 patients (30%; 95% confidence interval [CI], 10%–50%) had a major response to treatment (a complete response [CR] in 5% and a partial response [PR] in 25%). Seven patients (35%) had stable disease (SD). The median duration of response was 4.5 months (range, 1–9 months) and the disease control rate (CR + PR + SD) was 65%. The median survival was 11.5 months (range, 2–22 months) and the 1-year survival rate was 35%. The patients tolerated this regimen well, with only grade 3–4 neutropenia being observed in 6 patients (30%), anemia in 3 (15%), and thrombocytopenia in 1 (5%). The response rate to M-VAC in the first-line chemotherapy was significantly associated with the response to GP as the second-line chemotherapy. Conclusion  The combination of gemcitabine and paclitaxel is active and well tolerated as a second-line treatment in patients with advanced urothelial carcinoma.     

Second-line chemotherapy for advanced or recurrent endometrial carcinoma previously treated with paclitaxel and carboplatin, with or without epirubicin

Purpose

A combined chemotherapy of taxane and platinum, with or without anthracycline, has been used as a standard first-line regimen. The purpose of this study was to investigate the effectiveness of second-line chemotherapy for treatment of advanced or recurrent endometrial carcinoma previously treated with a combined chemotherapy of taxane and platinum, with or without anthracycline.

Methods

During the 2000?C2008 study period, 723 patients were diagnosed with endometrial cancer at the Departments of Obstetrics and Gynecology of the Osaka University and the Osaka Rosai Hospitals, Osaka, Japan. The subset of these cases that eventually required treatment by second-line chemotherapy was retrospectively analyzed.

Results

Response rate to second-line chemotherapy was 25%. Treatment-free interval (TFI) of ???or?<6?months was demonstrated to be significantly associated with the response to second-line chemotherapy (P?=?0.0026), progression-free survival (P?=?0.0003) and overall survival (P?=?0.025). The second-line chemotherapy similar to the first-line regimen was ineffective in all the 7 cases (100%) whose TFI was shorter than 6?months. Multivariate analysis showed that TFI was the most significantly important factor predicting the effectiveness of second-line chemotherapy (the adjusted hazard ratio of TFI on PFS and OS: 3.482, 95% CI, 1.641?C7.388, P?=?0.0012, and 2.341, 95% CI, 1.034?C5.301, P?=?0.042, respectively).

Conclusions

Our present study provides, for the first time, evidence that the majority of refractory or recurrent diseases, if they occur within 6?months of a first-line chemotherapy using taxane and platinum with or without anthracycline, are non-responsive to the current regimens of second-line chemotherapy.     

A phase II study of irinotecan and docetaxel combination chemotherapy for patients with previously treated metastatic or recurrent advanced gastric cancer

Purpose  Irinotecan (I) and docetaxel (D), each of which has a unique mechanism of action, were recently introduced in the treatment of patients with advanced gastric cancer (AGC). We have evaluated the efficacy and safety of the ID combination for AGC patients after failure of fluoropyrimidine- or platinum-based chemotherapy. Materials and methods  Patients with relapsed or progressive AGC after prior fluoropyrimidine- or platinum-based chemotherapy were treated with I (160 mg/m², 90 min) followed by D (65 mg/m², 1 h) every 3 weeks. Because of the unacceptable toxicity among the first ten patients, the doses were reduced for I (120 mg/m²) and D (50 mg/m²) every 3 weeks. Results  Forty-nine patients, of median age 53 years (range, 27–68 years), were treated with 170 cycles of chemotherapy (median, 2 cycles; range, 1–12 cycles). Three patients achieved complete response and seven achieved partial response, resulting in an overall response rate (ORR) of 20.4% [95% confidence interval (CI), 9.1–31.7%], with a median duration of 7.1 months (range: 2.1–69.1 months). ORR was 60% (95% CI, 29.6–90.3%) for the higher dose and 10.3% (95% CI, 0.7–19.8%) for the lower dose. Median time to progression for all patients was 2.7 months (95% CI, 1.7–3.8 months) and the median overall survival was 8.9 months (95% CI, 6.6–11.3 months). Grade 3/4 toxicities included neutropenia (90%), febrile neutropenia (50%), asthenia (40%), and diarrhea (10%) with the higher dose and neutropenia (71%), febrile neutropenia (11%), diarrhea (24%), and asthenia (24%) with the lower dose. There were two possible treatment-related deaths. Conclusion  The combination of irinotecan and docetaxel, once every three weeks shows anti-tumor activity but is not feasible as a second-line treatment for AGC patients after failure of fluoropyrimidine- or platinum-based chemotherapy due to the high rate of toxicities. S. J. Sym and H. M. Chang have contributed equally to this article.     

A retrospective analysis of the outcome of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck refractory to a platinum-based chemotherapy

AimsRecurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) develops in around 72 000 people in Europe every year. Treatment options are limited, mainly consisting of platinum-based palliative chemotherapy, with median overall survival times of only 6–8 months. No standard second-line treatment after progression on platinum-based chemotherapy is available. Few data have reported the efficacy of these treatments and the outcome of the patients. In an effort to generate such data, this retrospective study analysed clinical records from 151 patients with SCCHN refractory to platinum-based chemotherapy treated between 1990 and 2000 at seven different centres around Europe.Materials and methodsMost patients (45%) received only best supportive care (BSC), and had a median survival of 56 days. A total of 28.5% of the patients received second-line chemotherapies: 16.6% radiotherapy and 9.9% chemoradiotherapy.ResultsNo objective response was observed with the various second-line chemotherapies. The overall median survival was 103 days (95% confidence interval [CI]: 77–126 days) for the whole cohort. The overall objective response rate (ORR) to second-line treatment in this population was calculated to be 2.6%.ConclusionThese results highlight the need for additional treatment options for this disease. Similar, if not superior, response rates have already been observed in initial clinical studies of novel, targeted anti-cancer agents.     

A phase I study and pharmacologic evaluation of irinotecan and carboplatin for patients with advanced ovarian carcinoma who previously received platinum-containing chemotherapy

BACKGROUND: The objectives of the current study were to determine the maximum tolerated dose (MTD) of irinotecan and carboplatin in combination, to evaluate the efficacy and toxicity of the combination in patients with advanced ovarian carcinoma who previously received platinum-containing chemotherapy, and to examine the pharmacokinetics and pharmacodynamics of both drugs by using the Chatelut formula. METHODS: Patients with advanced ovarian carcinoma who previously received platinum-containing chemotherapy were treated with a combination of irinotecan and carboplatin. Carboplatin was administered as a 60-minute intravenous infusion on Day 1 and was followed by irinotecan, which was administered as a 90-minute intravenous infusion on Days 1, 8, and 15. Six dose levels of irinotecan (in mg/m(2))/carboplatin (mg . mL/min) were planned: 50 mg/m(2)/4 mg . mL/minute, 60 mg/m(2)/4 mg . mL/minute, 50 mg/m(2)/5 mg . mL/minute, 60 mg/m(2)/5 mg . mL/minute, 50 mg/m(2)/6 mg . mL/minute, and 60 mg/m(2)/6 mg . mL/minute. The carboplatin dosage was calculated by using the Chatelut formula. Treatment was repeated at 28-day intervals. RESULTS: In total, 19 patients in cohorts of 3 to 5 patients received irinotecan and carboplatin at 5 dose levels. The dose-limiting toxicities were Grade 4 neutropenia and Grade 4 thrombocytopenia. The MTD of the irinotecan/carboplatin combination was 60 mg/m(2)/5 . mg mL/minute. Partial responses were observed at higher dose levels. Pharmacologic studies demonstrated that administration of the dosage estimated with the Chatelut formula instead of the Chatelut formula with adjustment for serum creatinine resulted in a slightly excessive dose of carboplatin. CONCLUSIONS: The recommended dose for the Phase II study was irinotecan 60 mg/m(2) on Days 1, 8, and 15 with carboplatin 5 mg/mL . minute on Day 1 repeated every 4 weeks.     

Overview of the efficacy of cetuximab in recurrent and/or metastatic squamous cell carcinoma of the head and neck in patients who previously failed platinum-based therapies

BACKGROUND: The epidermal growth factor receptor (EGFR) inhibitor cetuximab is active in recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). The activity of cetuximab was compared with that of commonly used treatments in this setting. METHODS: All patients had recurrent and/or metastatic SCCHN and had progressed on cisplatin- or carboplatin-based chemotherapy. Efficacy data from 3 prospective studies (n=278 patients) that administered cetuximab as a single agent (n=103 patients) or combined with either cisplatin/carboplatin (n=96 patients) or cisplatin (n=79 patients) were compared with the results from a retrospective study of patients who received various second-line treatments (all treatments including best supportive care only, n=151 patients; chemotherapy, n=43 patients). Safety data considered were only those from the cetuximab studies. RESULTS: Over the 3 cetuximab trials, overall response rates from 10% to 13% and disease control rates from 46% to 56% were observed. The median time to disease progression ranged between 2.2 months and 2.8 months, and the median overall survival ranged between 5.2 months and 6.1 months. No patients who progressed on cetuximab alone responded to additional platinum. These survival data compared favorably with those from the retrospective study (median survival, 3.4 months [n=151 patients] and 3.6 months [n=43 patients]). Cetuximab-based treatments generally were tolerated well, and cetuximab did not increase the side effects associated with platinum therapy. CONCLUSIONS: Cetuximab has the potential to prolong survival in patients with recurrent and/or metastatic SCCHN who fail on platinum therapy compared with various second-line therapies. Cetuximab did not increase the toxicities associated with chemotherapy. The results obtained by treatment with cetuximab alone after platinum failure did not appear to differ from the results obtained by reintroducing platinum in combination with cetuximab.     

Excellent response to cis-platinum-based chemotherapy in patients with recurrent or previously untreated advanced nasopharyngeal carcinoma

Twenty-four patients with recurrent and/or locally advanced nasopharyngeal carcinoma who received cis-platinum-based chemotherapy are reported. Twelve patients with recurrent disease previously treated with radiotherapy received cis-platinum-based chemotherapy. An overall response rate of 67% (8/12) and a complete response (CR) of 25% (3/12) were achieved. All the CR patients were treated with cis-platinum and 5-fluorouracil (5-FU) infusion. Twelve patients with locally advanced (stage IV) previously untreated nasopharyngeal carcinoma received cis-platinum-based chemotherapy. Eight of those patients received cis-platinum and 5-FU combination chemotherapy followed by radiation therapy. An overall response of 75% (6/8) and a complete response of 50% (4/8) were achieved by induction chemotherapy. Subsequent radiation therapy to the 6 responding patients (CR 4, PR 2) to chemotherapy increased the complete response to 100% (6/6). The other two stable patients refused further therapy and died in less than 1 year from locoregional disease. Four patients were treated with concurrent cis-platinum and radiation therapy. A complete response of 100% (4/4) was achieved.     

Intraarterial chemotherapy with gemcitabine and cisplatin in locally advanced or recurrent penile squamous cell carcinoma

The prognosis of locally advanced or recurrent squamous cell carcinoma （SCC） of the penis after conventional treatment is dismal. This study aimed to evaluate the therapeutic effects of intraarterial chemotherapy with gemcitabine and cisplatin on locally advanced or recurrent SCC of the penis. Between April 1999 and May 2011, we treated 5 patients with locally advanced penile SCC and 7 patients with recurrent disease with intraarterial chemotherapy. The response rate and toxicity data were analyzed, and survival rates were calculated. After 2 to 6 cycles of intraarterial chemotherapy with gemcitabine and cisplatin, 1 patients with Iocoregionally advanced disease achieved a complete response, and 4 achieved partial response. Of the 7 patients with recurrent disease, 2 achieved complete response, 3 achieved partial response, 3 had stable disease, and 1 developed progressive disease. An objective tumor response was therefore achieved in 10 of the 12 patients. The median overall survival for the patients was 24 months （range, 10-50 months）. Three out of 10 patients who responded were long-term survivors after intraarterial chemotherapy. Intraarterial chemotherapy with gemcitabine and cisplatin may be effective and potentially curative in Iocoregionally advanced or recurrent penile SCC. The contribution of this therapy in the primary management of advanced or recurrent penile SCC shouJd be prospectively investigated.     

Prospective randomised phase II study of docetaxel versus paclitaxel administered weekly in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy.

BACKGROUND: Docetaxel and paclitaxel have activity in the second-line treatment of non-small-cell lung cancer (NSCLC), and can be administered as weekly schedules. This phase II randomised study was designed to test the efficacy and toxicity of both taxanes in patients with NSCLC previously treated with platinum-based chemotherapy. PATIENTS AND METHODS: Patients (n = 71) with documented NSCLC were randomised to receive docetaxel (n = 35 patients; 36 mg/m(2)) or paclitaxel (n = 36 patients; 80 mg/m(2)) as a 1 h weekly infusion for 6 weeks followed by a 2-week rest. The cycles were repeated until disease progression or non-acceptable toxicities occurred. RESULTS: Treatment achieved partial response of one versus five patients, median time-to-progression of 74 versus 68 days, and overall survival of 184 versus 105 days, with docetaxel and paclitaxel, respectively. The most common non-haematological toxicities were (docetaxel versus paclitaxel): grade 3/4 pulmonary toxicity in seven versus one patient; grade 2/3 diarrhoea in nine versus five; and grade 3/4 haematological toxicities occurred in two versus four patients. There were no treatment-related deaths. CONCLUSIONS: Docetaxel and paclitaxel administered weekly have discrete efficacy in patients with NSCLC previously treated with platinum-based chemotherapy. The higher non-haematological toxicity of docetaxel, particularly pulmonary toxicity and diarrhoea, is of concern and warrants further investigation.     

A phase II pharmacodynamic study of erlotinib in patients with advanced non-small cell lung cancer previously treated with platinum-based chemotherapy

PURPOSE: To examine potential markers of clinical benefit and the effects of erlotinib on the epidermal growth factor receptor (EGFR) signaling pathway in advanced non-small cell lung cancer patients refractory to platinum-based chemotherapy. EXPERIMENTAL DESIGN: Patients were given erlotinib (150 mg/d). Tumor biopsies were done immediately before treatment and in a subgroup of patients after 6 weeks' treatment. RESULTS: Of 73 evaluable patients, 7 (10%) had partial response and 28 (38%) had stable disease. In 53 patients with baseline tumor samples, no relationship was observed between pretreatment levels of EGFR, phosphorylated (p)-EGFR, p-AKT, p-mitogen-activated protein kinase (MAPK), or p27 and clinical benefit (i.e., response, or stable disease >/=12 weeks). Tumors from 15 of 57 patients had high EGFR gene copy number, assessed using fluorescence in situ hybridization (FISH positive), 10 of whom had clinical benefit, compared with 5 of 42 FISH-negative patients. FISH-positive patients had longer median progression-free [137 versus 43 days, P = 0.002; hazard ratio (HR), 0.37] and overall (226 versus 106 days, P = 0.267; HR, 0.70) survival than FISH-negative patients. In paired biopsy samples from 14 patients, p-EGFR (P = 0.002), p-MAPK (P = 0.001), and Ki-67 (P = 0.025) levels were significantly reduced after 6 weeks' treatment. Apoptosis was significantly increased in patients with clinical benefit (P = 0.029), and may be a marker of clinical benefit. CONCLUSION: In this study, EGFR FISH-positive status was associated with improved outcome after erlotinib therapy. Erlotinib led to reduced levels of p-EGFR, p-MAPK, and Ki-67, and stimulated apoptosis in tumor samples from patients with clinical benefit.     

Phase II study of docetaxel/vinorelbine in patients with non-small-cell-lung cancer previously treated with platinum-based chemotherapy

The aim of this phase II trial was to assess the efficacy and tolerability of docetaxel/vinorelbine as second-line therapy. Thirty-two patients with a performance status (PS) of 相似文献   

A retrospective analysis of 5-fluorouracil plus cisplatin as first-line chemotherapy in the recent treatment strategy for patients with metastatic or recurrent esophageal squamous cell carcinoma

Background

Patients with metastatic or recurrent esophageal squamous cell carcinoma (ESCC) have a poor prognosis. For decades, the most widely used first-line chemotherapy regimen for these patients has been the combination of 5-fluorouracil + cisplatin (CF). However, prognostic factors of CF as first-line chemotherapy for ESCC have not been clarified.

Methods

A total of 187 patients with metastatic or recurrent esophageal ESCC treated with CF at the National Cancer Center Hospital between January 2001 and December 2012 were enrolled in the study. The CF regimen comprised cisplatin (80 mg/m²) administered on day 1 and 5-fluorouracil (800 mg/m²) administered continuously on days 1–5, every 4 weeks. Multivariate Cox regression analysis was used to determine the potential prognostic factors.

Results

The median age of the patients was 62 (range 34–84) years. Metastasis and recurrence occurred in 116 and 71 of these patients, respectively. The overall response rate was 37.2%, with median progression-free and overall survival times of 4.8 and 10.4 months, respectively. In the multivariate analysis, higher serum C-reactive protein level and lower serum albumin level at the time of CF treatment initiation and number of metastatic sites were identified as independent prognostic factors for survival.

Conclusions

The results of this study corroborate previous findings on the efficacy of CF and will aid physicians in clinical decision-making and individual patient risk stratification, as well as in the further development of chemotherapy regimens.

     

Low-dose paclitaxel therapy as second-line chemotherapy for patients who previously received TS-1 therapy

TS-1 is often used as first-line chemotherapy for treatment of advanced or recurrent gastric cancer, but there is no definite therapeutic policy for patients for whom TS-1 is not effective, or to whom it cannot be administered. We have treated 6 patients with low-dose weekly paclitaxel therapy as second-line chemotherapy after initial treatment with TS-1. These patients consisted of 3 males and 3 females with a mean age of 56 years. Four patients had recurrent gastric cancer and two had unresectable advanced gastric cancer. Paclitaxel was administered in doses of 80 or 100 mg weekly. Adverse events more severe than grade 3 were not observed, but there were 2 cases of leukopenia (grade 1) and 2 cases of decreased hemoglobin (grade 2). Mean survival time after the administration of paclitaxel was 139 days. Five patients died of their cancer, and one is still alive 382 days after the paclitaxel administration. The one-year survival rate after administration was 16.7%. Low-dose weekly paclitaxel therapy is therefore safe and effective for patients with advanced and recurrent gastric cancer who previously received TS-1 therapy.     

Adjuvant chemotherapy with paclitaxel and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma

Objective:No standard postoperative adjuvant chemotherapy has ever been established in node-positive esophageal squamous cell carcinoma (ESCC).This is a study to explore the effect of postoperative paclitaxel (PTX) and cisplatin (DDP) in lymph node-positive,completely resected thoracic ESCC patients.Methods:We conducted a prospective phase Ⅱ trial.Patents had pathologically node-positive thoracic ESCC with negative margins.Outcomes of disease-free survival (DFS) and overall survival (OS) were compared with a matched historical control cohort.The postoperative chemotherapy regimen consisted of 4 to 6 cycles of PTX 150 mg/m2 administered intravenously on d 1 followed by DDP 50 mg/m2 on d 2 every 14 d.Results:Forty-three patients were accrued from December 2007 to May 2012 at Cancer Hospital of Chinese Academy of Medical Sciences for adjuvant chemotherapy.The historical control group consisted of 80 patients who received complete resection but no adjuvant chemotherapy during the same period of time.Of the 43 patients with adjuvant chemotherapy,37 (86.0％) patients completed 4 to 6 cycles of chemotherapy.The 3-year DFS rates were 56.3％ in the adjuvant group and 34.6％ in the control group (P=0.006).The 3-year OS rates were 55.0％ in the adjuvant group and 37.5％ in the control group (P=0.013).Multivariate analysis revealed that postoperative chemotherapy was the significant predictor for improved OS (P=0.005).Conclusions:Biweekly adjuvant PTX and DDP might improve 3-year DFS and OS in lymph node-positive,curatively resected thoracic ESCC patients.These conclusions warrant further study in randomized phase Ⅲ clinical trials.