Treatment of patients with advanced colorectal cancer with cisplatin, 5-fluorouracil, and leucovorin

Abstract

Based on in vitro studies that have demonstrated synergy between 5-fluorouracil (5-FU), leucovorin (LV), and cisplatin (CDDP) against human colon cancer cell lines, a clinical trial was initiated to determine the effects of this combination in patients with advanced unresectable colorectal carcinoma. Fifty-nine patients were enrolled in the study and 12 of them had received prior conventional 5-FU chemotherapy. Treatment consisted of 4 weekly courses of high-dose LV (200 mg/m2) administered by intravenous (IV) bolus, followed by 5-FU (550 mg/m2) and CDDP (20 mg/m2) each administered as a 2-hour infusion on 4 consecutive days. After a median of 5.5 treatment cycles, objective tumor response was seen in 20 of 59 patients (34%) (this included 3 complete remissions). The response rate in the 47 previously untreated patients was 38% (95% confidence limits, 26% to 53%). Stable disease occurred in 16 (27%) patients, whereas the tumor progressed in 23 (39%) patients. The median survival time was 11.5 months, with 15% of the patients alive at 2 years. The regimen was well tolerated and the primary side effects were mild and reversible gastrointestinal symptoms and myelosuppression. There was no episode of life-threatening toxicity. Eastern Cooperative Oncology Group (ECOG) Grade III adverse reactions that required 25% dose reductions occurred in only 14% of the patients. The results of this trial suggest that 5-FU, LV, and CDDP is an active, safe, and well-tolerated combination regimen in patients with advanced colorectal cancer.

Effect of cisplatin and c-myb antisense phosphorothioate oligodeoxynucleotides combination on a human colon carcinoma cell line in vitro and in vivo

“…For our study, we chose the LoVo Dx model because, if compared with the LoVo parental cell line, it presents a higher level of c-myb expression (Melani et al, 1991). Specifically, we investigated whether the inhibition of a growth-promoting gene such as cmyb affected the antineoplastic activity of cisplatin (CDDP), a chemotherapeutic agent widely used in the treatment of several solid human malignancies (Rosenberg, 1985), including colon carcinoma (Scheithauer et al, 1991;Rowinsky et al, 1991).…”

Randomized comparative study of surgical adjuvant chemotherapy using 5‐fluorouracil and dl‐leucovorin with CDDP, 5‐FU and dl‐leucovorin for advanced colorectal cancer

“…We have investigated the therapeutic and adverse effects of our protocol started in the early period after curative resection of stage II and III colorectal carcinoma. Scheithauer 1,10 studied a similar protocol in patients with advanced colorectal carcinomas and concluded that the protocol using three drugs, including CDDP for 4 days, showed a higher effective rate than 5‐FU/LV for 5 days, without a substantial difference in survival period.…”

“…Chemotherapy against advanced colorectal carcinoma using 5‐fluorouracil (5‐FU) in combination with other anticancer drugs has shown a biochemical modulation effect and has been used worldwide since the 1990 s 1–4 . Recently, CPT‐11 and oxaliplatin have become the first choice combined with 5‐FU + leucovorin (LV) for treatment of recurrent colorectal carcinoma 5,6 .…”

“…Over the past 5 years we have been performing a randomized clinical trial of surgical adjuvant chemotherapy using CDDP + 5‐FU + dl ‐LV (PFL therapy) in comparison with 5‐FU + dl ‐LV (FL therapy) for stage II and III colorectal carcinoma, expecting the single or dual biochemical modulation effect of 5‐FU 1,9,10 . We report our experience of these regimens for Japanese patients as soon as possible after the 14th postoperative day to advanced colorectal carcinoma with respect to side‐effects and survival.…”

Gene therapy for intraperitoneally disseminated pancreatic cancers by Escherichia coli uracil phosphoribosiltransferase (UPRT) gene mediated by restricted replication‐competent adenoviral vectors

“…To inhibit TS other anticancer drugs such as cisplatin (CDDP), leucovorin (LV) and methotrexate (MTX) are introduced as modulators of the essential cofactors for ternary complex formation 4. Although several reports have described a relatively high response rate in other cancers, such as gastric cancer and colorectal cancer,5, 6 the median survival time remains extremely short in pancreatic cancer when treated with such combined chemotherapy 7, 8…”