Nicolini A, Carpi A, Ferrari P, Sagripanti A, Anselmi L
Department of Internal Medicine, University of Pisa, Ospedale S Chiara, Italy.
Biomed Pharmacother. 1998;52(7-8):311-6. doi: 10.1016/s0753-3322(98)80027-9.
Data from 12 metastatic colorectal cancer patients who were submitted to a pilot study with a multistep subcutaneous (sc) low dose recombinant interleukin-2 (rIL-2), 5-fluorouracil (5-FU) and leucovorin (LV) administration were compared with those from 13 historical controls who were comparable for the major prognostic indices. All 12 patients in the pilot study were subjected initially to six to eight courses of 5-FU-LV by endovenous (ev) bolus consistent with the Machover schedule alternating with 6 weeks of rIL-2 cycles. At the progression of metastatic disease, the patients were given 500 mg/m2 per day of 5-FU by continuous infusion (ci) for 5 days every 4 weeks and in case of further progression, 2,600 mg/m2 of 5-FU by 24-h ci once a week for 6 weeks. The control patients were treated with 5-FU-LV by the Machover schedule until progression and then observed. As yet, two patients in the pilot study and three control patients are currently alive. In the pilot study, the patients' response rate (CR + PR) and overall response rate (CR + PR + SD) were much higher than in the controls (50 vs 23% and 92 vs 54%, respectively). Time duration of response and survival from primary surgery were more prolonged in the pilot study than in the historical control, although not significantly (10.5 vs 6 and 41.5 vs 29 months, respectively). Time from starting therapy to progression and survival from relapse were significantly in favour of the pilot study (11.5 vs 4 and 31 vs 13.5 months; P < 0.01 and P < 0.05 unpaired t-test, respectively). Low dose s.c. rIL-2 cycles were well tolerated and no interruption occurred. In the pilot study sporadic grade 3 toxicity (diarrhoea or leucopenia) was responsible for the reduction of 5-FU doses to 80% of the previous infusion, but no treatment was postponed. In conclusion, these preliminary data suggest the opportunity to initiate large prospective randomized trials using a multistep therapy with rIL-2, 5-FU ci at conventional and at high dose in metastatic colorectal cancer.
将12例接受多步骤皮下低剂量重组白细胞介素-2（rIL-2）、5-氟尿嘧啶（5-FU）和亚叶酸（LV）给药的转移性结直肠癌患者的数据，与13例在主要预后指标方面具有可比性的历史对照患者的数据进行了比较。试点研究中的所有12例患者最初按照马乔弗方案接受6至8个疗程的静脉推注5-FU-LV，并与6周的rIL-2周期交替进行。在转移性疾病进展时，患者每4周连续输注（ci）5天，每天给予500mg/m²的5-FU，若病情进一步进展，则每周1次24小时ci给予2600mg/m²的5-FU，持续6周。对照患者按照马乔弗方案接受5-FU-LV治疗直至病情进展，然后进行观察。目前，试点研究中有2例患者和3例对照患者仍存活。在试点研究中，患者的缓解率（CR+PR）和总缓解率（CR+PR+SD）远高于对照组（分别为50%对23%和92%对54%）。尽管差异不显著（分别为10.5个月对6个月和41.5个月对29个月），但试点研究中缓解持续时间和初次手术后的生存期比历史对照更长。从开始治疗到进展的时间以及复发后的生存期明显有利于试点研究（分别为11.5个月对4个月和31个月对13.5个月；分别采用非配对t检验，P<0.01和P<0.05）。低剂量皮下rIL-2周期耐受性良好，未发生中断。在试点研究中，偶发的3级毒性（腹泻或白细胞减少）导致5-FU剂量减至先前输注量的80%，但未推迟治疗。总之，这些初步数据表明，有机会开展大型前瞻性随机试验，在转移性结直肠癌中使用rIL-2、常规剂量和高剂量5-FU ci的多步骤疗法。
