Schallier D, Neyns B, Fontaine C, Steene J Vande, De Mey J, Meysman M, De Grève J
Department of Medical Oncology, Oncologisch Centrum, AZ-VUB, Laarbeeklaan 101, 1090 Brussels, Belgium.
Lung Cancer. 2007 May;56(2):247-54. doi: 10.1016/j.lungcan.2006.12.017. Epub 2007 Mar 6.
Phase II study of 3 cycles of triplet induction chemotherapy (response, toxicity) followed by radiotherapy in locally advanced non small cell lung cancer (NSCLC).
Patients with locally advanced inoperable non-small cell lung cancer are currently treated with concomitant or sequential chemotherapy and radiotherapy. However, the outcome of existing treatment modalities is unsatisfactory. Development of new strategies including more efficient systemic chemotherapy is warranted.
To study the antitumour activity and toxicity of a triplet combination of paclitaxel, carboplatin and gemcitabine as induction chemotherapy before radiotherapy, in locally advanced NSCLC and to evaluate time to progression and survival.
Three cycles of paclitaxel (175 mg/m(2) by 3h infusion on day 1), carboplatin (AUC 5mg/(mlmin) by IV bolus on day 1) and gemcitabine (1000 mg/m(2) by IV bolus on day 1 and 8) were administered every 3 weeks in reasonably fit patients. Fractionated radiotherapy with curative intent was initiated 4 weeks after the last chemotherapy administration. Toxicity was assessed weekly during cycle 1 and on day 1 and 8 in cycles 2 and 3. Response evaluation was performed at the end of cycle 3.
Forty-eight patients (20 stage IIIA and 28 stage IIIB) received a total of 134 cycles of chemotherapy. Forty-two patients received the intended 3 cycles. Thirty patients obtained an objective response (1 complete and 29 partial response) or 62.5% on the intent to treat analysis (95% confidence interval: 49-76%). None of the responders became eligible for surgery. The median time to progression and survival for all patients was 10.1 and 15.7 month, respectively. A significant difference was observed in survival parameters between stage IIIA and stage IIIB patients. Haematological toxicity grade 3/4, mainly neutropenia and thrombocytopenia, was most prominent on day 15 of the treatment cycles. Haematological support by means of recombinant erythropoietin, red blood cell or platelet transfusion, filgrastim administration or a combination was needed in 21 patients. None of the patients discontinued chemotherapy because of haematotoxicity. Grade 3/4 non-haematological toxicity leading to chemotherapy withdrawal occurred early during induction (2 and 1 in cycles 1 and 2, respectively).
Three cycles of the novel triplet combination of paclitaxel, carboplatin and gemcitabine (PACCAGE) is an active and feasible induction regimen for patients with locally advanced inoperable NSCLC. Neutropenia and to a lesser extent thrombocytopenia represent the main haematological toxicity. Whether this triplet regimen can improve outcome when compared to specific cisplatin doublet regimens should be evaluated in a phase III study.
对局部晚期非小细胞肺癌（NSCLC）进行3周期三联诱导化疗（疗效、毒性）后放疗的II期研究。
局部晚期无法手术的非小细胞肺癌患者目前接受同步或序贯化疗及放疗。然而，现有治疗方式的疗效并不理想。因此有必要开发包括更有效全身化疗在内的新策略。
研究紫杉醇、卡铂和吉西他滨三联组合作为放疗前诱导化疗在局部晚期NSCLC中的抗肿瘤活性和毒性，并评估疾病进展时间和生存期。
每3周为身体状况尚可的患者给予3周期化疗，具体为紫杉醇（第1天静脉滴注3小时，剂量175mg/m²）、卡铂（第1天静脉推注，剂量AUC 5mg/(ml·min)）和吉西他滨（第1天和第8天静脉推注，剂量1000mg/m²）。在最后一次化疗给药4周后开始进行根治性分割放疗。第1周期每周评估毒性，第2和3周期在第1天和第8天评估。在第3周期结束时进行疗效评估。
48例患者（20例IIIA期和28例IIIB期）共接受了134周期化疗。42例患者接受了计划的3周期化疗。30例患者获得客观缓解（1例完全缓解和29例部分缓解），意向性分析的缓解率为62.5%（95%置信区间：49 - 76%）。所有缓解者均不符合手术条件。所有患者的疾病进展时间中位数和生存期分别为10.1个月和15.7个月。IIIA期和IIIB期患者的生存参数存在显著差异。血液学毒性3/4级，主要为中性粒细胞减少和血小板减少，在治疗周期的第15天最为明显。21例患者需要通过重组促红细胞生成素、红细胞或血小板输注、非格司亭给药或联合使用进行血液学支持。没有患者因血液学毒性而停止化疗。导致化疗停药的3/4级非血液学毒性在诱导期早期出现（第1周期和第2周期分别为2例和1例）。
紫杉醇、卡铂和吉西他滨（PACCAGE）的新型三联组合进行3周期化疗是局部晚期无法手术的NSCLC患者的一种有效且可行的诱导方案。中性粒细胞减少以及程度较轻的血小板减少是主要的血液学毒性。与特定顺铂双联方案相比，该三联方案是否能改善疗效应在III期研究中进行评估。
