Galetta Domenico, Giotta Francesco, Rosati Gerardo, Gebbia Vittorio, Manzione Luigi, Di Bisceglie Maurizio, Borsellino Nicola, Colucci Giuseppe
Medical and Experimental Department, Oncology Institute of Bari, Via Hanhemann 10, 70126 Bari, Italy.
Anticancer Res. 2005 Nov-Dec;25(6C):4445-9.
The combination of cisplatin (CDDP) and 5-Fluorouracil (5-FU) is a standard regimen for the treatment of recurrent and metastatic head and neck squamous cell carcinoma (HNSCC). This combination shows a relevant toxicity and new chemotherapy associations with a more favourable toxicity profile are awaited. Carboplatin (CB) is a platinum derivative with less toxicity than CDDP. Raltitrexed (R) is a potent and specific thymidylate synthase inhibitor with activity comparable to that of 5-FU in colorectal cancer; moreover, it showed activity as a single agent in HNSCC.
Since 2001, a multicentre, phase II trial has been underway to evaluate the efficacy and toxicity of the CB+R combination in untreated patients with recurrent or metastatic HNSCC. Thirty-two patients were enrolled and included in an intent-to-treat analysis. Toxicity was graded according to NCI criteria. Patients had a histo/cytologically proven recurrent or metastatic HNSCC; patients with locally advanced disease not amenable to CDDP+5-FU treatment were also included. Patients had to be >18 years old with ECOG PS of 0-2 and adequate bone marrow, renal and liver functions. CB (AUC 5) and R (3 mg/m2) were administered intravenously every 3 weeks. The median age was 62 years (range 43-71), 29 M/3 F. The median PS was 1 (0-2). Twelve patients were staged III and 20 were metastatic (10 recurrent). The oral cavity/oropharynx were the primary site in 20 patients and the larynx in 10 patients. The median number of cycles delivered was 3, while globally 115 cycles were administered. The median time to progression was 4.2 months and median duration of survival was 9.8 months.
Seven patients achieved a partial response (22%), 10 patients showed a stable disease (31%), while 13 patients (48%) had progressive disease. Eight patients (25%) had a G 3-4 neutropenia, while G 3-4 anaemia was observed in 2 patients and thrombocytopenia in 1 patient. No extrar haematological G 3-4 toxicities were observed. A persistent G 2 hepatic toxicity led a patient to drop out from the study.
In our phase II trial, CB in combination with R showed a moderate activity with safe administration on an outpatient basis.
顺铂（CDDP）与5-氟尿嘧啶（5-FU）联合是治疗复发和转移性头颈部鳞状细胞癌（HNSCC）的标准方案。该联合方案显示出明显的毒性，因此期待有新的化疗联合方案，其毒性特征更有利。卡铂（CB）是一种铂类衍生物，毒性低于CDDP。雷替曲塞（R）是一种强效且特异性的胸苷酸合成酶抑制剂，在结直肠癌中的活性与5-FU相当；此外，它在HNSCC中作为单药显示出活性。
自2001年以来，一项多中心II期试验正在进行，以评估CB+R联合方案对未经治疗的复发或转移性HNSCC患者的疗效和毒性。32例患者入组并纳入意向性分析。毒性根据美国国立癌症研究所（NCI）标准分级。患者经组织学/细胞学证实为复发或转移性HNSCC；局部晚期疾病且不适用于CDDP+5-FU治疗的患者也被纳入。患者年龄必须>18岁，东部肿瘤协作组（ECOG）体能状态为0-2，骨髓、肾和肝功能良好。CB（曲线下面积[AUC]5）和R（3mg/m²）每3周静脉给药一次。中位年龄为62岁（范围43-71岁），男性29例/女性3例。中位体能状态为1（0-2）。12例患者为III期，20例为转移性（10例复发）。20例患者的原发部位为口腔/口咽，10例患者为喉。给药周期的中位数为3个，共给药115个周期。疾病进展的中位时间为4.2个月，中位生存期为9.8个月。
7例患者获得部分缓解（22%）,10例患者疾病稳定（31%），而13例患者（48%）疾病进展。8例患者（25%）出现3-4级中性粒细胞减少，2例患者出现3-4级贫血，1例患者出现血小板减少。未观察到非血液学3-4级毒性。1例患者因持续性2级肝脏毒性退出研究。
在我们的II期试验中，CB联合R显示出中度活性，可在门诊安全给药。
