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At least 325 records · Page 18Linked to original sources
PubMed2002

Less cytotoxicity to combination therapy of 5-fluorouracil and cisplatin than 5-fluorouracil alone in human colon cancer cell lines.

AIM: Our previous studies showed increased sensitivity to 5-FU in colon cancer cell lines with microsatellite instability, and considered that mutations of TGFbeta-R II, IGF IIR, RIZ gene might enhance the potentials of cell growth and proliferation, which increased the sensitivity to 5-FU. Here we compared the distribution of cell cycle and P53 status between two human colon cancer cell lines with different sensitivity to 5-FU. Because mechanistic differences exist between 5-FU and CDDP, we also analyzed the efficacy of CDDP and combination therapy on two human colon cancer cell lines. METHODS: We compared the sensitivity to CDDP of these two cell lines by MTT assay. Distribution of cell cycle under treatment of 5-FU, CDDP alone or both was analyzed by Flow Cytometry, and expression of P53 was detected by immunocytochemical staining. RESULTS: SW480 cells were more sensitive to CDDP than LoVo cells at the concentrations above 16 micromol/l (Ratio of absorption is 0.64 and 0.79 at 16 micromol/l, respectively; P<0.01). Efficacy of combination therapy was conversely lower than that of single-therapy of 5-FU (Ratio of absorption in LoVo+5-FU, SW480+5-FU, LoVo+5-FU+CDDP and SW480+5-FU+CDDP is 0.53, 0.54, 0.72, 0.78, respectively; P<0.01). LoVo cells were negative whereas SW480 cells positive in P53 expression. 5-FU induced G1-phase arrest in both cell lines, but LoVo cells peaked 24 hours earlier than SW480 cells, and 48 hours earlier for an apparent hypodiploid DNA. However, CDDP showed the contrary, inducing S-phase arrest, and SW480 cells peaking 36 hours earlier. Both cell lines showed hypodipliod nuclei 48 hours after CDDP treatment. Percentage of cells in G1-phase and S-phase dominated alternatively under combination therapy in both cell lines. CONCLUSION: These results suggest that colon cancer cells with microsatellite instability are more sensitive to 5-FU, whereas more resistant to CDDP. Combination therapy of 5-FU and CDDP shows fewer efficacies than 5-FU single-therapy, although it can render a cell cycle arrest. P53 may be involved in the shift of G1-phase to S-phase, but inessentially.

Adenocarcinoma↗
PubMed1991

Fluorouracil, doxorubicin, and cyclophosphamide versus fluorouracil, doxorubicin, and cyclophosphamide plus lonidamine for the treatment of advanced breast cancer: a multicentric randomized clinical study.

Experimental models have demonstrated the Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH)-potentiating activity of lonidamine. Phase II clinical trials on advanced breast cancer have shown that this drug induced a 16% objective response rate. Present multicentric randomized trial was conducted to verify whether lonidamine can potentiate the antineoplastic effects of conventional fluorouacil, Adriamycin, cyclophosphamide (FAC) chemotherapy in advanced breast cancer. From January 1987 to December 1989, 265 patients were enrolled in this study, and 231 are evaluable for response. After stratification according to institution and ECOG performance status (PS), the patients were randomly allocated to receive either standard FAC therapy (group A) or FAC plus lonidamine (600 mg orally daily three times a day) (group B). After three FAC courses, the patients with no progressive disease were further randomized to either receive continuous treatment up to the time of tumor progression (maximum: 10 courses) or to discontinue therapy when a response "plateau" was reached. In this latter group, the same therapy was restarted at relapse or disease progression. Objective response (complete response plus partial response) was significantly higher in group B (66.3%) compared to group A (42.3%). The actuarial median times to disease progression was also significantly longer (P less than 0.0001) in group B (median 9 months) than in group A (median 6 months). Other than myalgia and gastric pain, no increased toxicity was observed in the lonidamine. The analysis of second randomization are yet available because of the longer follow-up time required. Present findings suggest an interesting additive effect of lonidamine when combined with FAC chemotherapy and warrant further investigation in other therapeutic regimens and in other neoplastic diseases.

Adult↗
PubMed1987

A phase II trial of 5-fluorouracil and high-dose leucovorin in gastric carcinoma and a phase I trial of intraperitoneal 5-fluorouracil and leucovorin.

Twenty-five patients with advanced measurable gastric carcinoma were treated with D,L-leucovorin (CF) (500 mg/m2) administered as a 2-hour infusion and FUra (600 mg/m2) iv push midinfusion. Patients were treated weekly for 6 weeks followed by a 2-week rest. Median age was 57 (range 32 to 82). Median Eastern Cooperative Oncology Group (ECOG) performance status was 2 (range 0 to 4). Thirteen patients had progressed on previous combination chemotherapy that included FUra. At the time of this report, 19 patients were evaluable for response: 3 patients had partial responses, 8 had stable disease, and 8 progressed (but 3 of these received only 3 or fewer treatments before early disease-related death). Two of the responders were previously treated with FUra. Four patients were too early to evaluate. Measurable responses of greater than 50% were seen in bone, liver, lung, and an abdominal mass. Diarrhea occurred in 9 patients and FUra dose reduction was necessary in 8 of them. Other toxicities included lacrimation, rash, nausea, and mucositis. One toxic death occurred. Nine patients with gastrointestinal tumors confined primarily to the intra-abdominal space were treated with ip FUra in escalating doses (2 mM to 4 mM) in combination with D,L-CF in a 2-liter volume, either by 8 consecutive 4-hour dwells (7 patients) or once daily for 5 days (2 patients). The D,L-CF dose was 20.8 microM except for the first day of the 5-day schedule when it was 104 microM. Toxicity included leukopenia, mucositis, nausea and vomiting, skin rash, and abdominal pain. Three episodes of peritonitis resolved with antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Adriamycin, vincristine, cyclophosphamide and 5-fluorouracil (AVCF) compared with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in premenopausal breast carcinoma. Personal results.

Adjuvant treatment of breast cancer with AVCF gave significantly longer disease-free survival than CMF in the group of patients taken as a whole, in the subgroup with lymph node involvement and in the premenopausal subgroup. No significant difference was found regarding overall survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1979

Adriamycin, mitomycin C, and 5-fluorouracil in combination for advanced colorectal adenocarcinoma previously treated with 5-fluorouracil.

Twenty-one patients with progressing colorectal carcinoma previously treated with 5-FU were given a combination of 5-FU, adriamycin, and mitomycin C in an attempt to produce an objective response. No response was observed; 24% of patients had an arrest of their disease for a median of 18 weeks. 5-FU, adriamycin, and mitomycin C in combination failed to produce a response in patients with colorectal carcinoma previously treated with 5-FU.

Adenocarcinoma↗