Sprinzl Martin F, Wytopil Sonia M, Dahmen Anja, Kanzler Stephan, Galle Peter R, Moehler Markus
1st Medical Department, Johannes Gutenberg University, Mainz, Germany.
Clin Med Oncol. 2008;2:555-61. doi: 10.4137/cmo.s919. Epub 2008 Dec 3.
Despite many efforts to develop new chemotherapies for metastatic upper gastrointestinal (GI) cancer, overall prognosis continues to be fatal, particularly in gastric and pancreatic cancer. Many of these patients deserve second-or third-line treatment after failure of first-line chemotherapy. Therefore, we analysed toxicity and response rate of weekly docetaxel after failed upfront regimes in these upper GI cancer patients.
Between 2001 and 2006, 18 patients received docetaxel based regimes (35 mg/m(2) weekly) after informed consent. Response rates were determined using RECIST criteria or tumor progression if clinically evident. Toxicities were graded based on NCI CTC criteria (version 2). Most patients had gastric cancer (13/18). The remaining entities comprised of bilio-pancreatic cancer (5/18).
Docetaxel was administered as 2nd line therapy in 28% (5/18), 3rd line therapy in 56% (10/18) and 4th or 5th line therapy in 17% (3/18). The average docetaxel dose was 38 mg/m(2) (Median: 35 mg/m(2)) once weekly. Over a treatment duration of 14.7 weeks, the average dosage was 58 gr per patient and week. Overall, docetaxel was well tolerated with only few chemotherapy-associated toxicities (Grade 3/4), including nausea (17%), polyneuropathy (17%), anorexia (11%), neutropenia (6%) and leukopenia (17%). Docetaxel administration did not achieve any complete responses (CR) and one (5.6%) partial response (PR) was seen (1/18). In addition 5 patients (27.8%) had stable disease (SD), thus inducing a tumor control rate of 33.3% (6/18). Median progression-free survival was 2.4 months for all patients, 2.1 months in the gastric-cancer and 2.4 months in the bilio-pancreatic cancer subgroups respectively. After first docetaxel administration median survival for all patients was 4.5 months, patients with gastric cancer survived for 4.9 months whereas patients suffering from bilio-pancreatic carcinoma survived for 4.2 months. However, taken together 27% (5/18) had a remarkable overall survival of more than 2.5 years.
In severely pretreated patients, with documented chemoresistant GI tumors, weekly docetaxel was well tolerated, presented good tumor control rate and overall survival. Therefore, this regimen may be used as salvage treatment in individual patients with upper GI cancers.
尽管为转移性上消化道（GI）癌开发新的化疗方法付出了诸多努力，但总体预后仍然很差，尤其是在胃癌和胰腺癌中。这些患者中的许多人在一线化疗失败后值得接受二线或三线治疗。因此，我们分析了这些上消化道癌患者在前期治疗方案失败后每周使用多西他赛的毒性和缓解率。
2001年至2006年间，18例患者在获得知情同意后接受了基于多西他赛的治疗方案（每周35mg/m²）。根据RECIST标准或临床明显的肿瘤进展来确定缓解率。毒性根据NCI CTC标准（第2版）进行分级。大多数患者患有胃癌（13/18）。其余病例包括胆胰癌（5/18）。
多西他赛作为二线治疗给药的占28%（5/18），三线治疗的占56%（10/18），四线或五线治疗的占17%（3/18）。多西他赛的平均剂量为每周一次38mg/m²（中位数：35mg/m²）。在14.7周的治疗期间，平均剂量为每位患者每周58克。总体而言，多西他赛耐受性良好，仅有少数与化疗相关的毒性（3/4级），包括恶心（17%）、多发性神经病变（17%）、厌食（11%）、中性粒细胞减少（6%）和白细胞减少（17%）。多西他赛治疗未达到任何完全缓解（CR），仅观察到1例（5.6%）部分缓解（PR）（1/18）。此外，5例患者（27.8%）病情稳定（SD），因此诱导的肿瘤控制率为33.3%（6/18）。所有患者的无进展生存期中位数为2.4个月，胃癌亚组为2.1个月，胆胰癌亚组为2.4个月。首次给予多西他赛后，所有患者的中位生存期为4.5个月，胃癌患者存活4.9个月，而胆胰癌患者存活4.2个月。然而，总体而言，27%（5/18）的患者总生存期超过2.5年。
在经过充分预处理且有化疗耐药的胃肠道肿瘤患者中，每周使用多西他赛耐受性良好，具有良好的肿瘤控制率和总生存期。因此，该方案可作为个别上消化道癌患者的挽救治疗方法。
