Phase II Study of Paclitaxel and Carboplatin in Advanced Gastric Cancer Previously Treated with 5-Fluorouracil and Platinum

Chang, Heung Moon; Kim, Tae Won; Ryu, Baek-Yeol; Choi, Seo-Youn; Park, Yeon Hee; Lee, Jung Shin; Kim, Woo Kun; Kang, Yoon‐Koo

doi:10.1093/jjco/hyi077

Cited by 15 publications

(11 citation statements)

References 21 publications

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“…There were several possible explanations for improved treatment outcome over these periods. The proportion of patients who received sequential second-or third-line chemotherapy increased [36][37][38]. Although the role of salvage chemotherapy was not proven in advanced gastric cancer until the late 2000s, two recent phase III trials demonstrated the benefit of the second-line chemotherapy for the improvement of survival outcome in patients with advanced gastric cancer [6,7].…”

Section: Discussionmentioning

confidence: 99%

Improving trends in survival of patients who receive chemotherapy for metastatic or recurrent gastric cancer: 12 years of experience at a single institution

et al. 2014

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Background The aim of this retrospective study was to evaluate the changes in clinical features and treatment outcomes of the patients with metastatic or recurrent gastric cancer (MRGC) treated in the past 12 years. Results There were 880 patients (23 %) in period 1, 1573 (40 %) in period 2 and 1435 (37 %) in period 3. The most commonly used first-line chemotherapy regimen was fluoropyrimidine with/without platinum (72 %) for all periods. The use of second-and third-line chemotherapy was slightly but significantly more common in the two recent periods: 46 and 19 % in period 1, 54 and 26 % in period 2, and 53 and 27 % in period 3, respectively. Overall, 3494 patients (89.9 %) died with a median overall survival (OS) of 10.6 months (95 % CI 10.2-11.0). The OS was statistically significantly improved over the study period: 9.6 months (95 % CI 9.0-10.2) in period 1, 10.3 months (95 % CI 9.8-10.9) in period 2 and 11.7 months (95 % CI 11.0-12.4) in period 3 (p for trend \0.001). Multivariate analysis including eight prognostic factors (performance, gastrectomy, peritoneal/bone/lung metastasis, abnormal alkaline phosphatase/albumin/total bilirubin) showed that the more recent treatment period was an independent favorable prognostic factor for OS (p \ 0.001). Conclusion The OS of patients who receive chemotherapy for MRGC has been shown to improve over time.

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Section: Discussionmentioning

confidence: 99%

Improving trends in survival of patients who receive chemotherapy for metastatic or recurrent gastric cancer: 12 years of experience at a single institution

et al. 2014

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“…This synergy has led to the development of paclitaxelplatinum combination regimens in a number of solid tumors, including gastric cancer. Various phase II studies of 3-weekly paclitaxel-containing combinations in the treatment of patients with advanced gastric cancer are listed in Table 2 [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]. Combination regimens of paclitaxel plus platinum, or paclitaxel plus 5-FU, or both, yielded response rates of 32%-65% and MSTs of approximately 11 months (range, 6-14 months) in a fi rst-line treatment setting.…”

Section: Administration Of Paclitaxel Every 3 Weeks (3-weekly)mentioning

confidence: 99%

Paclitaxel chemotherapy for the treatment of gastric cancer

2009

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cause of cancer mortality. Although the incidence of gastric cancer has been declining in most developed countries, esophago-gastric junctional tumor and tumor in the cardia has, conversely, been increasing [2] and these tumors still remain one of the biggest problems worldwide.The prognosis of patients with advanced (i.e., unresectable or metastatic) gastric cancer is very poor. The median survival time for such patients is 6 to 9 months [3]. For many years, various chemotherapeutic agents have been used in attempts to improve survival, progression free-survival, response rate, and quality of life in patients with advanced gastric cancer as well as to improve disease-free survival in patients in whom curative resection of the cancers has been performed. 5-Fluorouracil (5-FU) and cisplatin-based regimens have long been considered reference treatments. Commonly used regimens have included epirubicin, cisplatin, and continuous infusion of 5-FU; 5 days' infusion of 5-FU plus cisplatin every 4 weeks; a weekly infusion regimen of 5-FU/leucovorin (LV) over 24 h plus cisplatin every 2 weeks; and 5-FU bolus plus 22-h infusion of 5-FU on days 1 and 2, in combination with cisplatin every 2 weeks. The results with these regimens, together with other study results, suggested that combination regimens including fl uorinated pyrimidines, cisplatin, doxorubicin, epirubicin, and methotrexate, had better response rates than single agents. Although gastric cancer is a relatively chemosensitive disease, with response rates of 30% to 40%, these treatments have shown a modest but unsatisfactory increase in overall survival [4]. In this regard, chemotherapy in the advanced gastric cancer setting is limited by a low complete response rate, response durations that are shortlived, and considerable toxicities.Nevertheless, recently, the development of new chemotherapeutic and molecular targeting agents has opened the door to various clinical trials to fi nd novel therapeutic strategies to improve the outcome of Abstract A comprehensive review of phase I and phase II clinical trials of paclitaxel and paclitaxel-containing chemotherapy regimens for advanced gastric cancer was performed. Response rates, median progression-free survivals, and median overall survivals were examined, together with the treatment regimens and the numbers of patients registered in each trial. Although paclitaxel monotherapy produced considerable improvement in tumor response and prognosis, combination doublet or triplet chemotherapy with fl uoropyrimidines and/ or platinum compounds showed better results than the paclitaxel monotherapy. With regard to the schedule of paclitaxel administration, weekly injection seemed to show less toxicity and better results than administration every 3 weeks. Adjuvant therapies, chemoradiation therapies, and paclitaxel treatment for gastric ascites were also investigated and are discussed.

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“…Paclitaxel (PTX; Figure 1) is a taxane that is derived from the bark of the Pacific yew tree Taxus brevifolia and was first shown to have anti-tumor activity in 1971 by Wani et al PTX may be used alone or in combination with other chemotherapy agents to treat many different types of cancer, including leukemia, lymphoma, and cancers of the head, neck, breast, esophagus, stomach, bladder, prostate, endometrium (uterus), and cervix (Wani et al, 1971;Rowinsky, 1993;Roth, 1995;McGuire et al, 1996;Seidman et al, 1996;Younes et al, 1997;Fountzilas et al, 1999;Kelly et al, 2001;Markman and Fowler, 2004;Chang et al, 2005;Ilson et al, 2007;Ward et al, 2007). The principal mechanism of its anti-cancer effect is to disrupt microtubule stability, thereby preventing cell growth (Schiff et al, 1979;Horwitz, 1980, 1981;Baum et al, 1981).…”

Section: Introductionmentioning

confidence: 99%

Paclitaxel induces apoptosis in leukemia cells through a JNK activation-dependent pathway

Peng¹,

Liu²,

Yao³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Paclitaxel (PTX) is a mitotic inhibitor widely used in chemotherapy for many types of cancers, including solid tumors and hematological malignancies. However, the molecular basis of the antiproliferation activity of PTX is not fully understood. In this paper, we focused on the role of c-Jun N-terminal kinase (JNK) pathways in PTXinduced apoptosis and proliferation inhibition. The effects of PTX were examined in human leukemia cell lines and patients' chronic lymphocytic leukemia (CLL) cells in relation to mitochondrial events, apoptosis, and perturbation of JNK activation using flow cytometry, siRNA, mitochondrial membrane potential determination, and western blotting. Exposure of cells to PTX at concentrations ≥10 nM for 18 or 24 h resulted in a significant release of cytochrome c from mitochondria to the cytosol, cleavages of procaspase 3 and poly (ADP-ribose) polymerase (PARP), and JNK activation, leading to apoptosis. The pan-caspase inhibitor BOC-D-FMK blocked the PTX-induced apoptosis but had no effect on cytochrome c release, suggesting that cytochrome c had been released before caspase activation. Moreover, both pharmacological JNK inhibitors SP600125 and JNK siRNA dramatically blocked PTX-induced apoptosis, cytochrome c release, caspase 3, and PARP cleavage. These findings demonstrate that JNK activation plays a critical role in the induction of apoptosis mediated by PTX in human leukemia cell lines and CLL patient-derived primary cancer cells, and this event is upstream of cytochrome c release, caspase 3, and PARP cleavage.

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Phase II Study of Paclitaxel and Carboplatin in Advanced Gastric Cancer Previously Treated with 5-Fluorouracil and Platinum

Abstract: Combination chemotherapy with paclitaxel and carboplatin is feasible in patients with advanced gastric cancer who were previously treated with 5-fluorouracil and platinum.

Cited by 15 publications

References 21 publications

Improving trends in survival of patients who receive chemotherapy for metastatic or recurrent gastric cancer: 12 years of experience at a single institution

Improving trends in survival of patients who receive chemotherapy for metastatic or recurrent gastric cancer: 12 years of experience at a single institution

Paclitaxel chemotherapy for the treatment of gastric cancer

Paclitaxel induces apoptosis in leukemia cells through a JNK activation-dependent pathway

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