A multicenter, randomized trial comparing efficacy and safety of paclitaxel/capecitabine and cisplatin/capecitabine in advanced gastric cancer

Abstract

BackgroundWe compared efficacy and safety of paclitaxel/capecitabine therapy followed by capecitabine for maintenance (PACX) versus cisplatin/capecitabine therapy (XP) in advanced gastric cancer.MethodsMulticenter, randomized, phase III trial was conducted in China (December 2009–February 2014). Adults (n = 320) with histologically confirmed, untreated metastatic/unresectable gastric or gastroesophageal junction adenocarcinoma; with ≥ 1 measureable lesions according to Response Evaluation Criteria in Solid Tumors 1.0 criteria; Karnofsky performance score ≥ 70 and life expectancy ≥ 3 months were randomized (1:1) to PACX or XP. PACX group received paclitaxel 80 mg/m2 intravenous on days 1 and 8; capecitabine 1000 mg/m2 orally BD on days 1–14, followed by a 7-day rest interval for 4 cycles, followed by maintenance capecitabine at same dosage/schedule until disease progression, unendurable adverse events or death. XP group received cisplatin intravenous 80 mg/m2 on day 1 and capecitabine at same dosage/schedule as PACX group per cycle for 6 cycles.ResultsMedian progression-free survival (5.0 versus 5.3 months; hazard ratio [95% CI]: 0.906; 0.706–1.164; p = 0.44) and overall survival (12.5 versus 11.8 months; hazard ratio: 0.878 [0.685–1.125]; p = 0.30) were not significantly different between PACX and XP groups. Objective response rate was significantly higher (43.1 versus 28.8%; p = 0.012) and disease control rate was similar (77.5 versus 72.5%; p = 0.75) in PACX versus XP, respectively. Quality of life was significantly improved in PACX versus XP after three treatment cycles. Many treatment-related adverse events were significantly lesser in PACX than XP.ConclusionsFirst-line chemotherapy with PACX is effective with milder toxicities in advanced gastric cancer, but could not replace XP.Electronic supplementary materialThe online version of this article (10.1007/s10120-018-0809-y) contains supplementary material, which is available to authorized users.

<p>Large Scale, Multicenter, Prospective Study of Apatinib in Advanced Gastric Cancer: A Real-World Study from China</p>

“…Combination of paclitaxel and capecitabine showed a mPFS of 5.0 months in first-line treatment in advanced gastric patients. 12 In the Chinese patient population analysis, the mPFS of capecitabine/cisplatin and 5-fluorouracil/cisplatin were 7.2 and 4.5 months, respectively. 13 In another phase III study, docetaxel and cisplatin plus fluorouracil were compared with cisplatin and fluorouracil, and the median time to progression was 5.6 and 3.7 months, respectively.…”

Identification of biomarkers predicting the chemotherapeutic outcomes of capecitabine and oxaliplatin in patients with gastric cancer

“…Chemotherapy resistance, whether primary or acquired, is common ( 6 ). The differences in molecular expression between tumors have resulted in different responses of patients with cancer to chemotherapeutic drugs ( 4 – 5 ). The accurate selection of chemotherapeutic drugs, which maximize the effectiveness of chemotherapy and reduce the toxic and side effects, is one of the most critical issues in the clinical application of chemotherapy ( 4 – 5 ).…”

“…Capecitabine is an oral preparation of antimetabolites that act specifically on tumor cells. After oral administration, capecitabine is rapidly absorbed through the intestinal mucosa and converted into 5-Fu through a three-step enzyme chain reaction in vivo (4). Capecitabine blocks the intracellular thymidine synthase from deoxyribonucleotide uridine and interferes with DNA synthesis (4).…”

“…After oral administration, capecitabine is rapidly absorbed through the intestinal mucosa and converted into 5-Fu through a three-step enzyme chain reaction in vivo (4). Capecitabine blocks the intracellular thymidine synthase from deoxyribonucleotide uridine and interferes with DNA synthesis (4). Oxaliplatin has stronger cytotoxic effect and fewer side effects compared with cisplatin and can bind to DNA after entering the nucleus (5).…”

Addition of Taxanes to Platinum and Fluoropyrimidines in Adjuvant Setting Did Not Improve Survival in Patients with Gastric Cancer after Curative Gastrectomy

“…In the present retrospective study, the addition of docetaxel or paclitaxel to the conventional combination of platinum and fluoropyrimidines in adjuvant chemotherapy for patients after curative gastrectomy did not demonstrate any benefit either in DFS or in overall survival. The addition of docetaxel or paclitaxel in chemotherapy regimens was shown to be effective in advanced gastric cancer [9][10][11]. For resectable gastric cancer, the results of the SAMIT study showed that sequential paclitaxel followed by fluoropyrimidines did not improve DFS compared to tegafur and uracil (UFT) or S-1 monotherapy [5].…”