Randomised phase II study comparing dose-escalated weekly paclitaxel vs standard-dose weekly paclitaxel for patients with previously treated advanced gastric cancer

• Published in: British journal of cancer 2014-01, Vol.110 (2), p.271-277
• Main Authors: Shitara, K, Yuki, S, Tahahari, D, Nakamura, M, Kondo, C, Tsuda, T, Kii, T, Tsuji, Y, Utsunomiya, S, Ichikawa, D, Hosokawa, A, Ishiguro, A, Sakai, D, Hironaka, S, Oze, I, Matsuo, K, Muro, K
• Format: Article
• Language: English
• Subjects: 631/154/109/1941; 692/699/1541; 692/699/67/1059/99; 692/699/67/1504/1829; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - adverse effects; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Chemotherapy; Clinical Study; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug dosages; Drug Resistance; Epidemiology; Female; Gastric cancer; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Hospitals; Humans; Male; Medical research; Medical sciences; Middle Aged; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neutropenia; Oncology; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Preventive medicine; Stomach Neoplasms - drug therapy; Stomach Neoplasms - mortality; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2013.726

Background: This randomised phase II trial compared dose-escalated weekly paclitaxel (wPTX) vs standard-dose wPTX for patients with previously treated advanced gastric cancer (AGC). Methods: Ninety patients were randomised to a standard dose of wPTX (80 mg m −2 ) or an escalated dose of wPTX (80–120 mg m −2 ) to assess the superiority of overall survival (OS) with a one-sided alpha error of 0.3 and a power of 0.8. Results: The median OS showed a trend towards longer survival in the dose-escalated arm (11.8 vs 9.6 months; hazard ratio (HR), 0.75; one-sided P =0.12), although it was statistically not significant. The median progression-free survival (PFS) was significantly longer in the dose-escalated arm (4.3 vs 2.5 months, HR, 0.55; P =0.017). Objective response rate was 30.3% with dose escalation and 17.1% with standard dose ( P =0.2). The frequency of all grades of neutropenia was significantly higher with dose escalation (88.7% vs 60.0%, P =0.002); however, no significant difference was observed in the proportion of patients experiencing grade 3 or more (40.9% vs 31.1%, P =0.34). Conclusion: Dose-escalated wPTX in patients with pretreated AGC met our predefined threshold of primary end point, OS ( P