Alternating irinotecan with oxaliplatin combined with UFT plus leucovorin (SCOUT) in metastatic colorectal cancer

Abstract

Tegafur -uracil (UFT) plus leucovorin s (LV, folinic acid) with alternating irinotecan and oxaliplatin were effective and well tolerated in patients with metastatic colorectal cancer (mCRC) in a phase I study. This study expanded the maximum tolerated dose group. Patients aged X18 years had histologically confirmed, inoperable, previously untreated, measurable mCRC. Patients received irinotecan 180 mg m À2 on day 1, oxaliplatin 100 mg m À2 on day 15 and UFT 250 mg m À2 plus LV 90 mg on days 1 -21 every 28 days. The phase I/II study comprised 45 patients, 29 at the maximum tolerated dose (MTD). The response rate in 38 evaluable patients was 63% (95% confidence interval (CI): 49 -80). Median time to progression and overall survival were 8.7 months (95% CI: 7.9 -10.4) and 16.8 months (95% CI: 9.6 -25.3), respectively. In the MTD group, one patient had grade 3 leucopaenia; one had grade 3 neutropaenia; three had grade 3 diarrhoea; and one had grade 3 neurotoxicity. No hand -foot syndrome grade 41 was seen. In total, 67% of eligible patients received second-line therapy. UFT plus LV with alternating irinotecan and oxaliplatin is an efficacious first-line treatment for mCRC, with minimal neurotoxicity and hand -foot syndrome.

Circulating Tumor Cell Enumeration in a Phase II Trial of a Four-Drug Regimen in Advanced Colorectal Cancer

“…Dosing was performed in accordance with the known maximum tolerated dose for this regimen. 15 Cetuximab 500 mg/m 2 was administered every 2 weeks. After treatment of the first 8 patients, the dose of cetuximab was reduced to 400 mg/m 2 because of an excess of National Cancer Institute Common Toxicity Criteria Adverse Events (NCI CTCAE, version 3.0) Grade 3 to 4 diarrhea and fatigue (see Supplemental Material in the online version).…”

“…However, in the clinical trial setting, only w60% of patients with ACRC have been fit enough to receive second-line treatment, and this has probably been even less in routine clinical practice. 14,15 Thus, administering the most efficacious and tolerable treatment upfront to patients with only "one chance" of systemic therapy is an important strategy and the central theme of the present study. Falcone et al 16 reported improved efficacy using the multidrug regimen FOLFOXIRI (oxaliplatin/irinotecan/5-FU) compared with FOLFIRI (irinotecan/5-FU) in the first-line treatment setting.…”

“…15 The rationale for alternating oxaliplatin and irinotecan was to allow recovery from the toxicity of each agent, reducing cumulative toxicity, but harnessing the benefit of using multiple agents. The regimen was well tolerated, with a RR of 68% and median OS of 19.6 months.…”

Caspase-mediated pro-apoptotic interaction of panaxadiol and irinotecan in human colorectal cancer cells

“…In addition, almost half of patients will die from recurrence of the cancer [3] . Previous studies have shown that chemotherapy toxicity could be reduced by chemoadjuvant compounds that potentiate the tumoricidal effects of lower doses [4–7] . Cancer treatment with botanicals such as American ginseng has received increasing attention in recent years [8–12] .…”

American ginseng berry enhances chemopreventive effect of 5-FU on human colorectal cancer cells

“…Drug-related adverse events not only worsen patients' quality of life, but can also lead to their refusal to continue chemotherapy (2,3). Chemotherapy-induced toxicity can be reduced by chemoadjuvant compounds that potentiate tumoricidal effects with lower doses (4)(5)(6). Identifying non-toxic chemo-adjuvants among herbal medicines may be an essential step in advancing the treatment of cancer (7).…”