Sequential therapy with methotrexate and 5-fluorouracil in the treatment of advanced colorectal carcinoma.

1986 ◽  
Vol 4 (1) ◽  
pp. 23-27 ◽  
Author(s):  
B A Leone ◽  
A Romero ◽  
M G Rabinovich ◽  
J E Perez ◽  
M Macchiavelli ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Tumor Regression ◽  
Sequential Therapy ◽  
Chemotherapeutic Agents ◽  
Optimal Time ◽  
High Dose ◽  
Time Interval ◽  
Major Objective ◽  
Duration Of Response ◽  
Advanced Colorectal Carcinoma

Twenty-nine patients with advanced colorectal carcinoma were entered in this study to evaluate the efficacy and toxicity of a sequential chemotherapeutic schedule with methotrexate (MTX), 200 mg/m2 intravenously (IV) (push injection) and 5-fluorouracil (5-FU), 1,200 mg/m2 in continuous IV infusion, using a 20-hour time interval. All patients received calcium leucovorin (LV), 25 mg, intramuscularly (IM) every six hours for eight doses beginning 24 hours after methotrexate administration. Courses were administered every 15 days. Of the 24 patients evaluable for response, 11 (46%) had major objective regressions (one complete remission [CR] and ten partial remissions [PR]). The survival rate of patients who responded to treatment was 60% at 16 months, whereas patients with no change and those in whom the disease progressed had a median survival of 9 months and 3 months, respectively. The median duration of response has not yet been reached in patients who presented objective tumor regression, and was 7.5 months in those with no change. Significant differences were found between objective regression and no change (P less than .0005) and between no change and tumor progression (P less than .05). All patients were evaluable for toxicity. There were three toxic-related deaths (10%) because of severe myelosuppresion, sepsis, and hemorrhage. These promising results, despite important toxicity, reveal the synergism between the two chemotherapeutic agents and also indicate that the response rate achieved could be a consequence of the 20-hour interval and high dose of 5-FU. Further studies are necessary to determine the optimal time interval and the adequate 5-FU dose.

A prospective randomized trial of 5-fluorouracil versus 5-fluorouracil and high-dose leucovorin versus 5-fluorouracil and methotrexate in previously untreated patients with advanced colorectal carcinoma.

1987 ◽  
Vol 5 (10) ◽  
pp. 1559-1565 ◽  
Author(s):  
N Petrelli ◽  
L Herrera ◽  
Y Rustum ◽  
P Burke ◽  
P Creaven ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Partial Response ◽  
Randomized Trial ◽  
Normal Saline ◽  
Colorectal Adenocarcinoma ◽  
High Dose ◽  
Treatment Regimens ◽  
Significant Difference ◽  
Duration Of Response ◽  
Advanced Colorectal Carcinoma

Seventy-four previously untreated patients with metastatic colorectal adenocarcinoma were prospectively randomized into one of three treatment regimens: (1) 5-fluorouracil (5-FU) 450 mg/m2 as an intravenous (IV) bolus daily for five days or toxicity, then 200 mg/m2 IV bolus every other day for six doses; (2) methotrexate (MTX) 50 mg/m2 in normal saline by IV infusion over four hours followed by an IV bolus of 5-FU 600 mg/m2. This was administered weekly for 4 weeks and then every 2 weeks. (3) Leucovorin 500 mg/m2 in a two-hour IV infusion of normal saline with 5-FU 600 mg/m2 as an IV bolus one hour after the Leucovorin began every week for 6 weeks. The combined complete and partial response rates in the three regimens were 11%, 5%, and 48%, respectively (P = .0009). The median duration of response in the 5-FU and Leucovorin regimen was 10 months. There was no statistically significant difference between the treatment regimens with respect to survival time (P = .6). Toxicity in the 5-FU and Leucovorin regimen was predominantly diarrhea (13 of 30 patients, 40%). In this regimen, eight of 13 patients (52%) who developed diarrhea not only required a dose reduction of 5-FU, but also hospitalization for IV hydration. The predominant toxicity in the 5-FU alone regimen and the 5-FU and MTX regimen was leukopenia. One drug-related death occurred in each regimen.

Treatment of advanced-stage colorectal adenocarcinoma with fluorouracil and high-dose leucovorin calcium: a pilot study.

1988 ◽  
Vol 6 (1) ◽  
pp. 142-146 ◽  
Author(s):  
J D Hines ◽  
M H Zakem ◽  
D J Adelstein ◽  
Y M Rustum
Keyword(s):  
Pilot Study ◽  
Colorectal Carcinoma ◽  
Median Survival ◽  
Stable Disease ◽  
Colorectal Adenocarcinoma ◽  
High Dose ◽  
Confidence Levels ◽  
Calcium Infusion ◽  
Advanced Colorectal Carcinoma ◽  
Leucovorin Calcium

Thirty-one evaluable patients with measurable advanced colorectal carcinoma were entered into a pilot study that used weekly fluorouracil (5-FU) at the dose of 600 mg/m2 by bolus infusion administered midway during a two-hour leucovorin calcium infusion of 500 mg/m2. This regimen was repeated weekly for six doses. Twenty-seven of these patients (87%) were considered to be refractory to prior 5-FU therapy and four (13%) were previously untreated. All 31 patients successfully completed at least one 6-week cycle of this regimen with acceptable toxicity. The combined complete (CR) and partial response (PR) rate was 45% with another 25% of patients remaining stable. The 95% confidence levels for the responding patients are 27.6% and 62.7%, respectively. The remaining 30% of the patients had all received prior 5-FU therapy and progressed. All of the responding patients and 80% of the patients with stable disease received two or more cycles of this regimen after a 3- to 4-week interval off therapy. The median time to disease progression was 16.1 months for responding patients and 6.7 months for those patients with stable disease. The median survival for the responders was 20.6 months and for those with stable disease 9.8 months. The median survival for the nonresponding patients was 3.9 months. Toxicity included diarrhea in 70% of patients, skin rash (erythema) in 10%, stomatitis in 15%, nausea and vomiting in 25%, and myelosuppression in 10%. This study confirms and extends previous observations that demonstrate the improved efficacy of 5-FU when used with high-dose leucovorin in advanced colorectal carcinoma.

A controlled evaluation of recent approaches to biochemical modulation or enhancement of 5-fluorouracil therapy in colorectal carcinoma.

1985 ◽  
Vol 3 (12) ◽  
pp. 1624-1631 ◽  
Author(s):  
T R Buroker ◽  
C G Moertel ◽  
T R Fleming ◽  
L K Everson ◽  
S A Cullinan ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Standard Therapy ◽  
Objective Response ◽  
Biochemical Modulation ◽  
High Dose ◽  
Combination Regimen ◽  
Measurable Disease ◽  
Advanced Colorectal Carcinoma ◽  
Controlled Evaluation ◽  
Combination Regimens

Three hundred thirty-five previously untreated patients with advanced colorectal carcinoma were randomly assigned to treatment with 5-fluorouracil (5-FU) alone, 5-FU plus N-(phosphonacetyl)-L-aspartic acid (PALA), 5-FU plus high-dose thymidine, 5-FU plus levamisole, or 5-FU plus methyl CCNU, vincristine, and streptozotocin (MOF-Strept). Dosages were designed to produce definite toxicity in the majority of patients, although the nature of dose-limiting reactions varied considerably among regimens. 5-FU alone and 5-FU plus levamisole produced mucocutaneous reactions, diarrhea, and leukopenia; 5-FU plus PALA produced primarily mucocutaneous reactions and diarrhea; 5-FU plus thymidine produced leukopenia with occasional neurotoxicity and hypotension; and MOF-Strept produced substantial nausea and vomiting with both thrombocytopenia and leukopenia. Objective response rates among patients with measurable disease varied from 12% (5-FU plus PALA) to 34% (MOF-Strept), but none of the regimens were significantly superior to 5-FU alone. Both interval to progression and survival were comparable among the five regimens with no reasonable chance that any combination regimen could produce as much as a 50% improvement when compared with 5-FU alone. Whereas we observed definite modulation of 5-FU dose--toxicity relationships, particularly with the thymidine and PALA combinations, this did not result in a detectable improvement in therapeutic effect. None of the combination regimens, administered in the dosages and schedules we used, can be recommended as standard therapy of advanced colorectal carcinoma.

Folinic acid plus high-dose 5-fluorouracil with allopurinol protection in the treatment of advanced colorectal carcinoma

1990 ◽  
Vol 26 (10) ◽  
pp. 1054-1056 ◽  
Author(s):  
N. Tsavaris ◽  
Ch. Bacoyannis ◽  
N. Milonakis ◽  
M. Sarafidou ◽  
N. Zamanis ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Folinic Acid ◽  
High Dose ◽  
Advanced Colorectal Carcinoma

scholarly journals A simplified regimen of weekly high dose 5-fluorouracil and leucovorin as a 24-hour infusion in patients with advanced colorectal carcinoma

Cancer ◽  
1999 ◽  
Vol 85 (9) ◽  
pp. 1925-1930 ◽  
Author(s):  
Tsai-Shen Yang ◽  
Kuan-Cheng Hsu ◽  
Jy-Ming Chiang ◽  
Reiping Tang ◽  
Jinn-Shium Chen ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
High Dose ◽  
Advanced Colorectal Carcinoma

WR-2721 and high-dose cisplatin: an active combination in the treatment of metastatic melanoma.

1987 ◽  
Vol 5 (4) ◽  
pp. 574-578 ◽  
Author(s):  
D Glover ◽  
J H Glick ◽  
C Weiler ◽  
K Fox ◽  
D Guerry
Keyword(s):  
Metastatic Melanoma ◽  
Phase I Trial ◽  
Progressive Disease ◽  
Phase Ii Trial ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Normal Tissues ◽  
Duration Of Response ◽  
Treatment Objective

Cisplatin, alone or in combination with other chemotherapeutic agents, is relatively inactive against metastatic melanoma. Prior trials have demonstrated partial response (PR) rates of less than 10% with cisplatin alone. WR-2721 is an organic thiophosphate compound, which in the animal model, selectively protects normal tissues against the toxicity of cisplatin chemotherapy. During the course of a phase I trial of WR-2721 and cisplatin, objective PRs were noted in patients with far advanced metastatic melanoma. These observations led us to perform a phase II trial of WR-2721 and cisplatin. Thirty-six patients received 128 courses of WR-2721 before cisplatin (60 to 150 mg/m2). All patients had progressive disease before treatment. Objective PRs were observed in 19 of 36 evaluable patients (53%). Three additional patients had minor responses (MRs). PRs occurred in 53% of patients with prior chemotherapy (ten of 19). Sites of responding metastases were subcutaneous disease (15 of 19 patients), lymph nodes (16 of 21 patients), lung (four of ten patients), and liver (eight of 17 patients). The median duration of response was 4 months, with a mean of 4.5 months (range, 1 to 8 months). Transient nephrotoxicity was observed in less than 5% of courses. In all cases, renal function returned to normal within 1 to 2 weeks. Hematologic toxicity was mild and infrequent. Nine patients developed peripheral neuropathy following a median cisplatin dose of 670 mg/m2. Twenty patients experienced mild clinical hearing loss. These data suggest that WR-2721 may potentiate the antitumor activity of cisplatin in metastatic melanoma.

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