Sun Weijing, Hewitt Maureen R, Theobald Marry R, Hershock Diane, Haller Daniel G
Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Cancer. 2007 Dec 15;110(12):2768-74. doi: 10.1002/cncr.23098.
The combination of a fixed dose rate (FDR) infusion of gemcitabine and irinotecan may have a synergistic effect in the treatment of patients with advanced and metastatic pancreatic and biliary cancer. The current study was conducted to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of the combination.
There were 32 patients with metastatic pancreatic and advanced unresectable/metastatic biliary adenocarcinoma who were entered into this open-label, phase 1 dose escalation trial. Gemcitabine was administered at an FDR of 10 mg/m(2)/minute intravenously (iv). Irinotecan was administered iv over 60 minutes after gemcitabine. Both gemcitabine and irinotecan were given on Days 1 and 8 of a 21-day cycle.
The MTD of the combination was gemcitabine at an FDR of 1200 mg/m(2) and irinotecan at a dose of 100 mg/m(2). The DLTs were neutropenia and neutropenic fever. Other DLTs included diarrhea, dehydration, and fatigue. Two patients developed deep venous thrombosis during the treatment. The efficacy of the combination was encouraging, even at the lower dose levels. Of 30 assessable patients, there was 1 complete response, 6 partial responses, and 16 patients with stable disease, with a response rate of 23%, a disease control rate of 76%, a median progression-free survival of 4.7 months, and a median overall survival of 7.0 months. The average number of treatment cycles received was 11.
The recommended doses of the combination for future study are gemcitabine at an FDR of 1200 mg/m(2) and irinotecan at a dose of 100 mg/m(2). The efficacy of the combination is encouraging. Further assessment of the combination with or without biologic agents is suggested.
吉西他滨与伊立替康固定剂量率（FDR）输注联合应用可能对晚期和转移性胰腺癌及胆管癌患者的治疗具有协同作用。本研究旨在确定该联合方案的剂量限制性毒性（DLT）和最大耐受剂量（MTD）。
32例转移性胰腺癌及晚期不可切除/转移性胆管腺癌患者进入这项开放标签的1期剂量递增试验。吉西他滨以10mg/m²/分钟的FDR静脉注射。伊立替康在吉西他滨给药后60分钟内静脉输注。吉西他滨和伊立替康均在21天周期的第1天和第8天给药。
该联合方案的MTD为吉西他滨FDR 1200mg/m²及伊立替康剂量100mg/m²。DLT为中性粒细胞减少和中性粒细胞减少性发热。其他DLT包括腹泻、脱水和疲劳。2例患者在治疗期间发生深静脉血栓形成。即使在较低剂量水平，该联合方案的疗效也令人鼓舞。30例可评估患者中，有1例完全缓解，6例部分缓解，16例病情稳定，缓解率为23%，疾病控制率为76%，无进展生存期中位数为4.7个月，总生存期中位数为7.0个月。接受的平均治疗周期数为11个。
未来研究推荐的联合方案剂量为吉西他滨FDR 1200mg/m²及伊立替康剂量100mg/m²。该联合方案的疗效令人鼓舞。建议进一步评估联合生物制剂与否的情况。
