为观察和比较多西他赛周方案给药联合5-氟尿嘧啶(5-FU)和顺铂(DDP)静脉化疗与多西他赛(DOC)、5-氟尿嘧啶静脉给药联合顺铂腹腔热灌注,治疗晚期胃癌患者的初步疗效和副反应,将90 例晚期胃癌患者,随机分入多西他赛、5-氟尿嘧啶和顺铂静脉化疗组或多西他赛、5 氟尿嘧啶静脉化疗联合顺铂腹腔热灌注化疗组,静脉化疗组45 例,热灌注化疗组45 例.研究表明,静脉化疗组有效率为44.4%(20/45),热灌注化疗组为66.7%(30/45),其中完全缓解(CR)1 例,有统计学差异(P=0.038);临床受益反应(CBR)评估,静脉化疗组有效率为64.4%(29/45),热灌注化疗组为82.2%(37/45),差异有统计学意义(P=0.0458);两组副反应主要为骨髓抑制,胃肠道反应,神经毒性等,无统计学差异.多西他赛周方案、5-氟尿嘧啶联合顺铂腹腔热灌注化疗方案治疗晚期胃癌近期疗效优于单存静脉化疗,两组副反应相似,耐受性良好.
This study aims to observe and compare the efficacy and side effect of weekly docetaxel combined with 5-fluorouracil and cisplatin intravenous treatment and weekly docetaxel plus 5-fluorouracil intravenous combined with intraperitoneal perfusion (CHPP) with cisplatin treatment. Ninety patients with advanced gastric cancer were randomized into intravenous chemotherapy group (45 patients) who received docetaxel 36 mg/m2, iv, 1wk×3wk, CF 200 mg/m2, iv, d1-5, 5-Fu 500 mg/m2, iv, d1-5, DDP 25 mg/m2, iv, d1-3, repeated every four weeks for two cycles and intravenous chemotherapy plus CHPP group (45 patients) who received docetaxel 36 mg/m2, iv, 1wk× 3wk, CF 200 mg/m2, iv, d1- 5, 5- FU 500 mg/m2, iv, d1- 5, DDP 75 mg/m2, CHPP, d1, and abdomen hyperthermia treatment with radiofrequency. The results show that all patients were assessable for response in intravenous chemotherapy group and CHPP group. The overall response rate of intravenous chemotherapy group was 44.4%. The response rate of CHPP group was 66.7%, including one CR. There was statistical difference between two groups (P=0.038). The clinical beneficial response (CBR) in intravenous chemotherapy group and CHPP group were 64.4% and 82.2%, respectively. There was apparent statistical difference (P=0.0458). The major toxicities were myelosuppression, nausea/vomiting and neurotoxicity. There was no significant difference in side effect between the two groups. Docetaxel administered by weekly infusion plus 5-fluorouracil combined with hyperthermic intraperitoneal perfusion chemotherapy with cisplatin in the treatment of advanced gastric cancer is more effective than intravenous treatment. The side effect of two groups was similar. CHPP therapy was well tolerated.
[1] Parkin D M, Bray F, Ferlay J, et al. Global cancer statistics, 2002[J]. CA: A Cancer Journal for Clinicians, 2005, 55(2): 74-108.
[2] Harima Y, Nagata K, Harinma K, et al. A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage III cervical carcinoma[J]. International Journal of Hyperthermia, 2001, 17(2): 97-105.
[3] van der Zee J, Gonzalez G D, van Rhoon G C, et al. Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: A prospective, randomised, multicentre trial[J]. Lancet, 2000, 355(9210): 1119-1125.
[4] Wendtner C M, Abdel R S, Krych M, et al. Response to neoadjuvant chemotherapy combined with regional hyperthermia predicts long-term survival for adult patients with retroperitoneal and visceral highrisk soft tissue sarcomas[J]. Journal of Clinical Oncology, 2002, 20(14): 3156-3164.
[5] Hildebrandt B, Wust P, Ahlers O, et al. The cellular and molecular basis of hyperthermia[J]. Critical Reviews in Oncology/Hematology, 2002, 43 (1): 33-56.
[6] Urano M, Kuroda M, Nishimura Y. For the clinical application of themochemotherapy given at mild temperatures[J]. International Journal of Hyperthermia, 1999, 15(2): 79-107.
[7] Burris H, Moore M J, Anderson J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line theraphy for patients with advanced pancreas cancer:a randomized trial[J]. Journal of Clinical Oncology, 1997, 15(4): 2403-2413.
[8] Facchiano E, Scaringi S, Kianmanesh R, et al. Laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of malignant ascites secondary to unresectable peritoneal carcinomatosis from advanced gastric cancer[J]. European Journal of Surgical Oncology, 2008, 34(2): 154-158.
[9] Armstrong D K, Bundy B, Wenzel, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer[J]. New England Journal of Medicine, 2006, 354(1): 34-43.
[10] Takiuchi, Goto M, Kawabe S, et al. Second-line chemotherapy in gastric cancer[J]. Gan To Kagaku Ryoho, 2005, 32(1): 19-23.
[11] Wagner A D, Grothe W, Haerting J, et al. Chemotherapy in advanced gastric cancer: A systematic review and meta analysis based on aggregate data[J]. Journal of Clinical Oncology, 2006, 24(18): 2903-2909.
[12] Giuliani F, Gebbia V, De V F, et al. Docetaxel as salvage therapy in advanced gastric cancer: A phase Ⅱ study of the Gruppo Onclogico Italia Meridiongale (G. O. I. M)[J]. Anticancer Research, 2003, 23 (56): 4219-4222.
[13] Bang Y J, Kang W K, Kang Y K, et al. Docetaxel 75 mg/m2 is active and well tolerated in patients with metastatic or recurrent gastriccancer: A phase II trial[J]. Japanese Journal of Clinical Oncology, 2002, 32(7): 248-254.
[14] van C E, Moiseyenko V M, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer, a report of the V325 study group[J]. Journal of Clinical Oncology, 2006, 24 (31): 4991-4997.
[15] Lorenzen S, Hentrich M, Haberl C, et al. Split-dose docetaxel, cisplatin and leucovorin/fluorouracil as first- line therapy in advanced gastric cancer and adenocarcinoma of the gastroesophageal junction: Results of a phase II trial[J]. Annals of Oncology, 2007, 18(10): 1673-1679.
[16] Song C W, Park H J, Lee C K, et al. Implications of increased tumor blood flow and oxygenation caused by mild temperature hyperthermia in tumor treatment[J]. International Journal of Hyperthermia, 2005, 21 (8): 761-767.
[17] Ahmed K, Zhao Q L, Matsuya Y, et al. Enhancement of macrosphelideinduced apoptosis by mild hyperthermia[J]. International Journal of Hyperthermia, 2007, 23(4): 353-361.
[18] Brozovic A, Simaga S, Osmak M. Induction of heat shock protein 70 in drug-resistant cells by anticancer drugs and hyperthermia[J]. Neoplasma, 2001, 48(2): 99-103.
