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At least 19 recordsLinked to original sources

PubMed1988

Sensitivity test for 5-fluorouracil and its analogues, 1-(2-tetrahydrofuryl)-5-fluorouracil, uracil/1-(2-tetrahydrofuryl)-5-fluorouracil (4:1) and 1-hexylcarbamoyl-5-fluorouracil, using the subrenal capsule assay.

The chemosensitivity of 20 human neoplastic tissues including 13 gastric and 7 colorectal cancers was tested using 5-fluorouracil (5-FU) and its analogues: 1-(2-tetrahydrofuryl)-5-FU (FT), uracil/FT (UFT) and 1-hexylcarbamoyl-5-FU (HCFU), and the in vivo subrenal capsule (SRC) assay. The relative variation of tumor size (delta TS/TSo) was calculated as follows: delta TS/TS0 = (TS6-TS0/TS0) x 100%, where TS6 was the tumor size on day 6 and TS0 on day 0, and the chemosensitivity was considered to be sensitive when delta TS/TS0 in the treated group was decreased to below -10%. The mean tumor size was -10.9 +/- (SD) 10.9% for 5-FU, -12.3 +/- 17.1% for FT, -18.4 +/- 15.8% for UFT and -17.9 +/- 15.4% for HCFU. The decrease of tumor size was marked when exposed to UFT (p less than 0.01) or HCFU (p less than 0.02), compared with that to 5-FU. Positive correlations were noted between the tumor sizes of 5-FU and its analogues (5-FU vs. FT, r = 0.851; 5-FU vs. UFT, r = 0.746; 5-FU vs. HCFU, r = 0.685). In 9 tissues resistant to 5-FU, 2 (22%) were sensitive to FT, 4 (44%) to UFT, 5 (56%) to HCFU and 7 tissues (78%) to at least one of these analogues. These results suggest that the SRC assay is useful for predicting the effective drug among 5-FU and 5-FU analogues, for individual patients with cancer.

Animals↗

PubMed1985

A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma. Fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin.

Three hundred five patients with advanced pancreatic and gastric carcinoma were randomly assigned to treatment with fluorouracil, fluorouracil plus doxorubicin (Adriamycin) (FA), or fluorouracil plus doxorubicin plus mitomycin (mitomycin C) (FAM). All regimens were equivalent with regard to patient survival. There is no reasonable likelihood that either the FA or FAM regimen could produce a meaningful survival advantage over fluorouracil alone. Interval to disease progression, objective response rates, and palliative effects (improved performance, body weight, or symptoms) were essentially equivalent among the three regimens. With regard to toxicity, the FAM regimen produced more anorexia, nausea, vomiting, leukopenia, thrombocytopenia, and cumulative bone marrow suppression. Fluorouracil alone produced more stomatitis and diarrhea. Because of a failure to produce improved survival or palliation, unrewarded toxicity, and excessive cost, neither the FA nor FAM regimen can be recommended for the treatment of advanced pancreatic or gastric cancer.

Adenocarcinoma↗

PubMed1988

UFT is more antineoplastic against gastric carcinoma than 5-fluorouracil, 1-(2-tetrahydrofuryl)-5-fluorouracil and 1-hexylcarbamoyl-5-fluorouracil.

The sensitivity of human gastric cancer tissue to 5-fluorouracil (5-FU) and its analogues 1-(2-tetrahydrofuryl)-5-fluorouracil (FT), UFT and 1-hexylcarbamoyl-5-fluorouracil (HCFU) was determined, using the in vivo subrenal capsule (SRC) assay. The relative variation of tumor size (delta TS/TS0) was calculated as follows: delta TS/TS0 = (TS6-TS0/TS0) x 100%, where TS6 was the tumor size on day 6 and TS0 on day 0. The chemosensitivity was considered to be positive when delta TS/TS0 in the treated group decreased to below -10%. For their cytotoxic effects, 5-FU analogues are converted to 5-FU and positive correlations were noted between the tumor sizes of 5-FU and its analogues (5-FU vs. FT, r = 0.737; 5-FU vs. UFT, r = 0.653; 5-FU vs. HCFU, r = 0.709), in gastric tissues from 22 patients. The means +/- SD of tumor size were -8.5 +/- 11.5% for 5-FU, -8.3 +/- 16.0% for FT, -18.1 +/- 15.8% for UFT and -13.7 +/- 13.4% for HCFU. Decrease in tumor size was marked in case of exposure to UFT, compared with that to 5-FU (p less than 0.001), FT (p less than 0.001) and HCFU (p less than 0.05). 18% were sensitive to UFT and resistant to 3 other drugs. Thus, UFT proved to be the most effective among 5-FU and its analogues for decreasing the size of gastric cancer tissues.

Animals↗

PubMed1989

Effects of the plasma concentration of 5-fluorouracil and the duration of continuous venous infusion of 5-fluorouracil with an inhibitor of 5-fluorouracil degradation on Yoshida sarcomas in rats.

The correlations of the 5-fluorouracil (5-FU) level in the plasma and the duration of continuous 5-FU infusion with the antitumor activity of 5-FU on Yoshida sarcomas in rats were examined. The circadian variation in the plasma level of 5-FU during continuous infusion was prevented by treatment with 3-cyano-2,6-dihydroxypyridine (CNDP), which strongly inhibits 5-FU degradation. On continuous venous infusion of 2 to 30 mg/kg of 5-FU over 24 h with CNDP at a molar ratio of 1:10 into normal rats, the 5-FU level in the blood was linearly proportional to the dose of 5-FU. The optimum schedule for antitumor activity on Yoshida sarcomas in rats was found to be infusion of 5-FU at 5 mg/kg over 24 h for 6 consecutive days, which gave a plasma 5-FU level of 176 ng/ml. Continuous infusion of 5-FU to give a plasma level of 300 ng/ml for 6 consecutive days from day 5 after implantation of tumor cells, when the tumors weighed about 1.0 g, resulted in complete regression of the tumors in all rats.

Animals↗

PubMed1987

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.

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.

Adenocarcinoma↗

PubMed1989

Treatment of patients with advanced colorectal carcinomas with fluorouracil alone, high-dose leucovorin plus fluorouracil, or sequential methotrexate, fluorouracil, and leucovorin: a randomized trial of the Northern California Oncology Group.

We compared the effectiveness of fluorouracil (5-FU) alone (arm A), high-dose leucovorin plus 5-FU (arm B), and sequential methotrexate, 5-FU, and leucovorin (arm C) for treatment of patients with advanced colorectal carcinomas who had not received prior chemotherapy. Arm A consisted of infusions of 5-FU at 12 mg/kg/d intravenously (IV) for 5 days followed by weekly infusions of 5-FU at 15 mg/kg; arm B consisted of leucovorin infusions at 200 mg/m2/d IV plus infusions of 5-FU at 400 mg/m2/d IV on days 1 through 5 of a 28-day cycle; arm C consisted of methotrexate at 50 mg/m2 orally every 6 hours for five doses followed by infusions of 5-FU, 500 mg/m2 IV, and leucovorin, 10 mg/m2 orally, every 6 hours for five doses every other week. A total of 265 patients were entered into the trial, of whom 249 (94%) were fully evaluable. The objective response rate (complete [CR] plus partial [PR] responses) was 17.3% on arm A, 18.8% on arm B, and 19.8% on arm C (log-rank test, P greater than .4). The median time to failure was 138 days on arm A, 166 days on arm B, and 182 days on arm C (log-rank test, P values of arm A v B = .06; arm A v arm C = .04). Median survival was 345 days on arm A, 324 days on arm B, and 356 days on arm C (log-rank test, P greater than .4). Treatment with 5-FU alone was significantly more dose intensive and more toxic than either of the experimental combinations. The rates of grade 3 or greater nonhematologic toxicity were 42.3% on arm A, 24.3% on arm B, and 14.3% on arm C. Hematologic toxicity was milder but had the same pattern. This study indicates that these regimens of high-dose leucovorin plus 5-FU and sequential methotrexate, 5-FU, and leucovorin are not more effective than is 5-FU alone for treatment of patients with colorectal carcinomas when 5-FU is administered at high-dose intensity.

Adult↗

PubMed1987

A Northern California Oncology Group randomized trial of leucovorin plus 5-fluorouracil versus sequential methotrexate, 5-fluorouracil, and leucovorin in patients with advanced colorectal cancer who failed treatment with 5-fluorouracil or 5-fluorodeoxyuridine alone.

The current study was initiated to confirm preliminary reports that 20% or more of patients with colorectal cancer who fail treatment with 5-fluorouracil (FUra) will respond to treatment with either leucovorin plus FUra or with sequential methotrexate, FUra, leucovorin. One hundred two patients with advanced, measureable colorectal cancer who failed treatment with FUra and/or 5-fluorodeoxyuridine (FUdR) were randomized to treatment with either high-dose leucovorin plus FUra (Arm B) or sequential methotrexate, FUra, leucovorin (Arm C). In this interim report, 92 patients were evaluable for toxicity and 89 patients were evaluable for response. Grade 3 or 4 nonhematologic toxicity which was primarily gastrointestinal was experienced by 25% of patients on both treatment arms during at least 1 treatment cycle. Hematologic toxicity was minimal. Among 43 evaluable patients on Arm B, there were 2 complete responses (5%) and 1 minor response (3%). Among 46 evaluable patients on Arm C, there was 1 complete response (2%), 1 partial response (2%), and 6 minor responses (14%). The median time to treatment failure was 2.2 months on Arm B and 3.5 months on Arm C. The median survival was 8.3 months on Arm B and 8.7 months on Arm C. Colorectal cancers that are resistant to FUra are cross-resistant to both experimental combinations.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1979

Antitumor activity of alkylesters of 1-beta-D-ribofuranosyl-5-fluorouracil-5'-phosphate against murine lymphoma L5178Y resistant to 1-beta-D-ribofuranosyl-5-fluorouracil.

A 1-beta-D-ribofuranosyl-5-fluorouracil-resistant clone, designated L5178Y/FUR, was established in this experiment. This is one of the colonies derived from a subculture which acquired resistance to 1-beta-D-ribofuranosyl-5-fluorouracil by passaging the L5178Y cells through four sucessive episodes of culture in Fischers' medium containing 1-beta-D-ribofuranosyl-5-fluorouracil; each analog treatment was followed by recovery intervals. In this subline, IC99 values for 1-beta-D-ribofuranosyl-5-fluorouracil was 0.57 muM, which was 24 times as great as in the parent line (0.0024 muM), and this subline showed a cross resistance to 5-fluorouracil. New alkylesters of 1-beta-D-ribofuranosyl-5-fluorouracil 5'-phosphate (FUMP-alkylesters) were synthesized and their antitumor activity was examined against 1-beta-D-5-fluorouracil-sensitive and -resistant L5178Y sublines. Only hexadecylester of 1-beta-D-ribofuranosyl-5-fluorouracil 5'-phosphate was effective, not only to 1-beta-D-ribofuranosyl-5-fluorouracil line but also to 1-beta-D-ribofuranolsyl-5-fluorouracil-resistant subline. Other compounds showed cross resistant in the 1-beta-D-ribofuranosyl-5-fluorouracil-resistant cells.

Animals↗

PubMed1986

Prodrugs of 5-fluorouracil. V. 1-Alkoxycarbonyl derivatives as potential prodrug forms for improved rectal or oral delivery of 5-fluorouracil.

The hydrolysis and physicochemical properties of seven 1-alkoxycarbonyl derivatives of 5-fluorouracil were studied to assess their potential as prodrugs with the aim of enhancing the delivery characteristics of the parent drug. All derivatives were hydrolyzed to quantitatively yield 5-fluorouracil. The pH-rate profiles for the hydrolysis were measured. The rates of hydrolysis were markedly accelerated in the presence of plasma, affording half-lives of hydrolysis less than 4 min in 80% human plasma. The derivatives were more lipophilic than 5-fluorouracil but the aqueous solubility was only slightly reduced or, for one derivative, even greater than that of 5-fluorouracil. A preliminary absorption study in rabbits showed an absolute bioavailability of 5-fluorouracil of 100% following rectal administration of 1-(butoxycarbonyl)-5-fluorouracil as compared with no absorption following administration of 5-fluorouracil itself. The potential utility of the prodrug derivatives to enhance the oral and/or rectal delivery of the parent drug is suggested.

Animals↗

PubMed1991

5-Fluorouracil dose intensity increase in 5-fluorouracil and leucovorin combination: results of a phase II study.

It was our intention to verify if in the combination of 5-fluorouracil and leucovorin, the fluoropyrimidine dose intensity is an important determinant of response as noted by Hryniuk when 5-fluorouracil was given alone. By employing the Machover regimen but with cycles repeated every three weeks, a 5-fluorouracil projected dose intensity of 616 mg/m2/wk was obtained. It approximates the maximum tolerated dose for this drug when used alone by i.v. bolus. 50 patients entered this study and 48 were evaluable for response and toxicity. The overall response rate was 29% (five complete responses and nine partial responses). The dose limiting toxicity was gastrointestinal rather than myelosuppression. 5-fluorouracil dose reduction was needed in seven patients. The mean delivered dose intensity of 5-fluorouracil was 610 mg/m2/wk (582 mg/m2/wk in patients in whom 5-fluorouracil was reduced for toxicity and 616 mg/m2/wk in the others). Our results do not seem to show any advantage in the maximization of 5-fluorouracil dose intensity. Furthermore, in an analysis of data from the literature we did not find any difference in response rate in relation to dose intensity in the 5-fluorouracil/leucovorin combination.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1977

Comparative studies on the metabolism of 2-(tetrahydrofuryl)-5-fluorouracil and 5-fluorouracil.

5=Fluorouracil inhibited DNA synthesis markedly using various DNA precursors such as deoxyuridine, orotic acid, uracil, and uridine except for thymidine. 2-(Tetrahydrofury)-5-fluorouracil (FT-207) did not inhibit DNA synthesis with any of the precursors tested. The metabolisms of 5-fluorouracil and FT-207 in mice and rats were studied. When administered intravenously 5-fluorouracil was rapidly degraded to fluoro-beta-alanine in both mice and rats, while at most 70% of FT-207 was slowly degraded after a prolonged period. The metabolites of FT-207 were found to be 5-fluorouracil and fluoro-beta-alanine in both species of animals. In vitro degradation of FT-207 into 5-fluorouracil was observed mainly in the microsomal fraction in the presence of NADPH. This result suggested that microsomal electron-transport system was concerned with the degradation of FT-207.

Alanine↗

PubMed1989

Fluorouracil Filtering Surgery Study one-year follow-up. The Fluorouracil Filtering Surgery Study Group.

Two hundred thirteen patients participated in the Fluorouracil Filtering Surgery Study, a randomized clinical trial, to determine the efficacy and safety of subconjunctivally injected 5-fluorouracil after filtering surgery in eyes with poor prognoses. Twenty-eight (27%) of the 105 eyes in the 5-fluorouracil group and 54 (50%) of the 108 eyes in the standard group were classified as failures, defined by reoperation for control of intraocular pressure during the first year or an intraocular pressure greater than 21 mm Hg at the one-year visit (P = .0007, Mantel-Haenszel chi-square). Corneal epithelial toxicity and transient visual acuity loss were more common in the 5-fluorouracil group (P less than .001, chi-square); however, the visual acuities and the mean visual field sensitivities were not significantly different at one year. We recommend the use of subconjunctivally injected 5-fluorouracil after trabeculectomy in eyes with uncontrolled glaucoma and poor prognoses, specifically after previous cataract extraction or unsuccessful filtering surgery.

Adult↗

PubMed1991

Unusual serpentine hyperpigmentation associated with 5-fluorouracil. Case report and review of cutaneous manifestations associated with systemic 5-fluorouracil.

A variety of cutaneous reactions have been reported with the use of systemic 5-fluorouracil. Our patient had serpentine hyperpigmented streaks appearing 5 days after bolus infusion of 5-fluorouracil. The patient also had other skin eruptions, that is, inflammation of actinic keratoses and folliculitis limited to the forehead; these reactions have been reported previously with 5-fluorouracil medication. We report this case and review the literature on skin manifestations associated with 5-fluorouracil therapy.

Adenocarcinoma↗

PubMed1978

Studies on antitumor agents, 2. Syntheses and antitumor activities of 1-(tetrahydro-2-furanyl)-5-fluorouracil and 1,3-bis(tetrahydro-2-furanyl)-5-fluorouracil.

Convenient and efficient methods were developed for preparing 1-(tetrahydro-2-furanyl)-5-fluorouracil (Thf-FU, 3) [trade name, Futraful (Ftorafur) or FT-207], which is used clinically as an antitumor agent, and 1,3-bis(tetrahydro-2-furanyl)-5-fluorouracil (Thf2-FU, 4). For the syntheses, 2,4-bis(trimethylsily)-5-fluorouracil (Me3Si-FU, 1) and 2-acetoxytetrahydrofuran (Thf-OAc, 2) were condensed in the presence of Friedel-Crafts catalysts, such as SnCl4 and BF3-Et2O in dichloromethane, or in the presence of NaI in acetonitrile to give Thf-Fu or Thf2-FU depending on the reaction conditions and workup procedure. A trace of 3-(tetrahydro-2-furanyl)-5-fluorouracil (3-Thf-FU, 5) was formed in these reactions. Thf2-FU was easily hydrolyzed to Thf-FU. 2-Methoxytetrahydrofuran can be used instead of Thf-OAc for preparation of Thf-FU under similar conditions. The optimal ratios of Me3Si-FU, Thf-OAc, and SnCl4 or NaI for preparation of Thf-FU and Thf2-FU were determined. In all cases, 2-2.5 equiv of Thf-OAc with respect to Me3Si-FU gave the best results. The yields of Thf-FU and more especially of Thf2-FU were greatly dependent on the relative amount of SnCl4, and 0.01-0.1 equiv of the catalyst with respect to Me3Si-FU gave the best results. Thf2-FU was found to be effective against murine solid tumors and it was less toxic than Thf-FU when given orally. The antitumor activity of 3-Thf-FU is also reported.

Animals↗

PubMed1989

19F NMR of 5-fluorouracil-substituted transfer RNA transcribed in vitro: resonance assignment of fluorouracil-guanine base pairs.

5-Fluorouracil is readily incorporated into active tRNA(Val) transcribed in vitro from a recombinant phagemid containing a synthetic E. coli tRNA(Val) gene. This tRNA has the expected sequence and a secondary and tertiary structure resembling that of native 5-fluorouracil-substituted tRNA(Val), as judged by 19F NMR spectroscopy. To assign resonances in the 19F spectrum, mutant phagemids were constructed having base changes in the tRNA gene. Replacement of fluorouracil in the T-stem with cytosine, converting a FU-G to a C-G base pair, results in the loss of one downfield peak in the 19F NMR spectrum of the mutant tRNA(Val). The spectra of other mutant tRNAs having guanine for adenine substitutions that convert FU-A to FU-G base pairs all have one resonance shifted 4.5 to 5 ppm downfield. These results allow assignment of several 19F resonances and demonstrate that the chemical shift of the 19F signal from base-paired 5-fluorouracil differs considerably between Watson-Crick and wobble geometry.

Anticodon↗

PubMed1989

[Randomized multicenter trial of sequential methotrexate and 5-fluorouracil versus 5-fluorouracil alone in advanced gastric cancer].

In a recent phase II trial we have shown a favorable response rate for sequential methotrexate-5-fluorouracil (MF) in advanced gastric and colorectal cancer. We determined the therapeutic effect of sequential MF in patients with advanced gastric cancer by comparing it to 5-fluorouracil alone (F) in a randomized multicenter trial. Since February 1987 to July 1988, 133 patients with advanced gastric cancer have been prospectively randomized to receive either MF (methotrexate 100 mg/m2 i.v. push, 5-fluorouracil 600 mg/m2 i.v. drip over 15 minutes one hour after methotrexate and leucovorin 15 mg p.o. q 6 hrs x 2 beginning 24 hrs after methotrexate) of F (the same 5-fluorouracil as described for MF). Each treatment was repeated weekly x 5, then q 2 weeks. The two treatment arms were balanced for 17 clinical characteristics. The response rate was 17.9% (10 of 56 patients) in the MF arm and 1.9% (one of 53 patients) in the F arm (p less than 0.01). Median duration of response was 6.8 weeks (MF) and 6 weeks (F), respectively. Median survival time was 7.9 months (MF) and 7.3 months (F) on interim findings. Leukocytopenia and GI toxicity were significantly more common in patients receiving MF, but the degree was similar for both arms. Other side effects were minimal and no different. This schedule of MF is more effective than F in inducing remission for patients with advanced gastric cancer.

Adult↗

PubMed1977

A model for prediction of chemotherapy response to 5-fluorouracil based on the differential distribution of 5-[18F]fluorouracil in sensitive versus resistant lymphocytic leukemia in mice.

The distribution of 5-[18F]fluorouracil has been compared in two variants of the same tumor in c57bL X DBA/2 F1 mice: solid L1210 lymphocytic leukemia tumor susceptible to 5-fluorouracil treatment and the same tumor, made resistant to the drug over a 34-generation span. Significant differences in 5-[18F]fluorouracil distribution were observed, most notably in the tumor:blood ratios at 12 hr postinjection. The drug-responsive tumor showed a 20:1 concentration ratio, whereas the drug-resistant tumor only had a 4:1 concentration ratio. We postulate that these differences, observed here in this animal tumor model, may be a reflection of similar ratio differences in humans. This technique may allow, by noninvasive quantification of tumor:blood ratios following administration of 5-[18F]fluorouracil to man, the differentiation of those human tumors that are likely to respond to drug therapy from those in which the response will be minimal or nil.

Animals↗

PubMed1978

Chemotherapy of advanced measurable colon and rectal carcinoma with oral 5-fluorouracil, alone or in combination with cyclophosphamide or 6-thioguanine, with intravenous 5-fluorouracil or beta-2'-deoxythioguanosine or with oral 3(4-methyl-cyclohexyl)-1(2-chlorethyl)-1-nitrosourea: a Phase II-III study of the Eastern Cooperative Oncology Group (EST 4273).

In a randomized multi-institutional trial of the Eastern Cooperative Oncology Group, 316 patients with advanced measurable colorectal adenocarcinoma were treated with a weekly schedule of 5-fluorouracil given orally and intravenously with oral-5-fluorouracil in combination with cyclophosphamide or 6-thioguanine, or with oral Methyl CCNU administered once every eight weeks. On failure or progression, 133 protocol patients crossed-over to a secondary therapy, while 116 other patients previously treated with 5-fluorouracil off protocol were randomized to treatment with Methyl CCNU or B-2'-deoxythioguanosine. Response rates among patients who had received no prior chemotherapy were 18% to oral 5-FU, 15% to intravenous 5-FU and to MeCCNU, 12% to 5-FU and 6-thioguanine and 5% to cyclophosphamide and 5-FU, with little activity (3% response rate) in crossover or previously treated patients. Treatment with 5-FU, particularly oral 5-FU was associated with the least drug-related toxicity. Hematologic toxicity was greatest with Methyl CCNU, but was no more frequent in previously treated than in untreated patients. A tendency toward cumulative bone marrow depression was noted. 5-FU was effective only in ambulatory patients, whereas responses among non-ambulatory patients were seen only in the group treated with Methyl-CCNU.

Adenocarcinoma↗