Kliche Kay-Oliver, Kubsch Konstantin, Raida Martin, Masri-Zada Rami, Höffken Klaus
Department of Internal Medicine II, Friedrich-Schiller University, Erlanger Allee 101, 07740 Jena, Germany.
J Cancer Res Clin Oncol. 2002 Sep;128(9):516-24. doi: 10.1007/s00432-002-0363-0. Epub 2002 Aug 21.
To study efficacy and tolerability of chronomodulated (CM)-chemotherapy in patients with metastatic or locally advanced tumors of the GI tract. Furthermore, calcium folinate was replaced by sodium folinate due to better feasibility.
We treated 79 patients with metastatic or locally advanced colorectal cancer ( n=52), cancer of the pancreas/biliary tract ( n=14), and other malignancies ( n=14) with a total of 592 courses of CM-therapy. Out of the total study population 53/79, i.e., 67.1% had received prior chemotherapy. Most of the patients (77.2%) received sodium-folinate-5-FU-oxaliplatin-CM (SOFOX-CM) as first-line chronomodulated therapy, 20.3% received sodium-folinate-5-FU-irinotecan-CM (SOFIRI-CM), and 2.5% ( n=1) received sodium-folinate-5-FU-gemcitabine-CM (SOFGEM-CM).
We found a moderate overall toxicity with grade 3-4 neuropathy in 7.46% of patients during a total of 433 courses of SOFOX-CM and grade 3-4 diarrhea in 10.26% of patients after 154 courses of SOFIRI-CM. SOFOX-CM had to be stopped only in one patient due to grade 3-4 sensory neuropathy. CM-therapy led to complete response (CR) in 1.3%, partial response (PR) in 15.2%, stable disease (SD) in 32.9%, and progressive disease (PD) in 44.3% of all patients. For the 26 chemonaive patients remission data were as follows: CR one patient (3.8%), PR four patients (15.4%), SD seven patients (26.9%), PD 12 patients (46.3%), lost to follow-up one patient (3.8%), and too-early-for-analysis one patient (3.8%). The median progression-free-survival (PFS) was 4 months (range, 0-24 months). The median PFS was also 4 months (range, 0-21 months) for those patients receiving SOFOX-CM as first CM-therapy ( n=61), while it was found to be 0 months (range, 0-10 months) for patients ( n=16) receiving SOFIRI-CM as first chronomodulated therapy.
We found CM-therapy to be effective and safe in the treatment of advanced malignancies of the GI tract. Sodium folinate offers superior feasibility and compatibility with cytostatic drugs without drawbacks.
研究时辰调节（CM）化疗对胃肠道转移性或局部晚期肿瘤患者的疗效和耐受性。此外，由于可行性更好，亚叶酸钙被亚叶酸钠替代。
我们用总共592个疗程的CM疗法治疗了79例转移性或局部晚期结直肠癌患者（n = 52）、胰腺癌/胆管癌患者（n = 14）和其他恶性肿瘤患者（n = 14）。在整个研究人群中，53/79（即67.1%）曾接受过化疗。大多数患者（77.2%）接受亚叶酸钠-5-氟尿嘧啶-奥沙利铂-CM（SOFOX-CM）作为一线时辰调节疗法，20.3%接受亚叶酸钠-5-氟尿嘧啶-伊立替康-CM（SOFIRI-CM），2.5%（n = 1）接受亚叶酸钠-5-氟尿嘧啶-吉西他滨-CM（SOFGEM-CM）。
我们发现总体毒性中等，在总共433个疗程的SOFOX-CM治疗期间，7.46%的患者出现3 - 4级神经病变，在154个疗程的SOFIRI-CM治疗后，10.26%的患者出现3 - 4级腹泻。仅1例患者因3 - 4级感觉神经病变而停止SOFOX-CM治疗。CM疗法使所有患者中1.3%达到完全缓解（CR），15.2%达到部分缓解（PR），32.9%疾病稳定（SD），44.3%疾病进展（PD）。对于26例初治患者，缓解数据如下：CR 1例患者（3.8%），PR 4例患者（15.4%），SD 7例患者（26.9%），PD 12例患者（46.3%），失访1例患者（3.8%），过早无法分析1例患者（3.8%）。中位无进展生存期（PFS）为4个月（范围0 - 24个月）。对于那些接受SOFOX-CM作为首次CM疗法的患者（n = 61），中位PFS也是4个月（范围0 - 21个月），而对于接受SOFIRI-CM作为首次时辰调节疗法的患者（n = 16），中位PFS为0个月（范围0 - 10个月）。
我们发现CM疗法在治疗胃肠道晚期恶性肿瘤方面有效且安全。亚叶酸钠具有更好的可行性以及与细胞毒性药物的兼容性，且无缺点。
