Combination chemotherapy using cyclophosphamide, vincristine, methotrexate, 5-fluorouracil, and prednisone in solid tumors

Bearden, James D.; Coltman, Charles A.; Moon, Thomas E.; Costanzi, John J.; Saiki, John H.; Balcerzak, Stanley P.; Rivkin, Saul E.; Morrison, Francis S.; Lane, M. Daniel; Spigel, Stuart C.

doi:10.1002/1097-0142(197701)39:1<21::aid-cncr2820390105>3.0.co;2-i

Cited by 5 publications

(2 citation statements)

References 6 publications

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“…This combination seems to be more effective and well-tolerated since minimal or no toxicity was observed in 47% of tested patients and 51% had mild side effects. The best response was observed in ovarian cancer patients, 45% of which responded at least partially [ 67 ]. The rationale for the beneficial administration of vincristine with methotrexate is based on the fact that vincristine potently increases the uptake of methotrexate into cells and makes the methotrexate treatment more effective [ 68 ].…”

Section: Combination Of Vincristine With Methotrexatementioning

confidence: 99%

Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics

Škubník

Pavlíčková

Ruml

et al. 2021

Biology

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Treatment of blood malignancies and other cancer diseases has been mostly unfeasible, so far. Therefore, novel treatment regimens should be developed and the currently used ones should be further elaborated. A stable component in various cancer treatment regimens consists of vincristine, an antimitotic compound of natural origin. Despite its strong anticancer activity, mostly, it cannot be administered as monotherapy due to its unspecific action and severe side effects. However, vincristine is suitable for combination therapy. Multidrug treatment regimens including vincristine are standardly applied in the therapy of non-Hodgkin lymphoma and other malignancies, in which it is combined with drugs of different mechanisms of action, mainly with DNA-interacting compounds (for example cyclophosphamide), or drugs interfering with DNA synthesis (for example methotrexate). Besides, co-administration of vincristine with monoclonal antibodies has also emerged, the typical example of which is the anti-CD20 antibody rituximab. Although in some combination anticancer therapies, vincristine has been replaced with other drugs exhibiting lesser side effects, though, in most cases, it is still irreplaceable. This is strongly evidenced by the number of active clinical trials evaluating vincristine in combination cancer therapy. Therefore, in this article, we have reviewed the most common cancer treatment regimens employing vincristine and bring an overview of current trends in the clinical development of this compound.

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Section: Combination Of Vincristine With Methotrexatementioning

confidence: 99%

Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics

Škubník

Pavlíčková

Ruml

et al. 2021

Biology

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“…Cancer of the large bowel is refractory to treatment with chemotherapeutic agents whether administered either singly [1][2][3] or in combination [4][5][6]. One explanation for this phenomenon may be a general lack of sensitivity of such tumors to cytotoxic agents that are diverse in their mechanisms of action.…”

Section: Introductionmentioning

confidence: 99%

Biochemical mechanisms in colon xenografts: Thymidylate synthase as a target for therapy

Houghton

Hazelton

et al. 1989

Invest New Drugs

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Growth of human adenocarcinomas of the colon and rectum in immunoincompetent mice has allowed for a greater understanding of the interaction of 5-fluorouracil, its metabolism, and mechanism(s) of cytotoxicity under conditions of tumor growth in situ. Conversely, this agent has proven to be a useful tool in defining metabolic characteristics in human colon adenocarcinomas. Analysis of tumor sensitivity to 5-fluorouracil (FUra),5-fluorouridine (FUrd) and 5-fluoro-2'-deoxyuridine (FdUrd) suggests that growth inhibition in vivo is related to a DNA-directed event. Resistance, de novo appears to be a consequence of relatively transient inhibition of the target enzyme thymidylate synthase (dTMP-synthase), which may be a consequence of low concentrations of 5,10-methylenetetrahydrofolate (CH2-H4PteGlu) or its polyglutamate forms within tumor cells in situ. In order to study the relationship between inhibition of dTMP-synthase and growth inhibition, mutant cells deficient in their ability to salvage dThd have been selected, and grown as xenografts. Data suggest that transient inhibition of dTMP-synthase and not dThd salvage is responsible for resistance de novo, and that prolonged inhibition of dTMP-synthase would be a lethal event in vivo. This would predict that a cell lacking dTMP-synthase activity would not be tumorigenic. This has been tested directly by selecting clones of GC3 colon adenocarcinoma cells deficient in dTMP-synthase (TS-) activity. Preliminary data indicate that each of 3 TS- clones is tumorigenic in athymic nude mice. The importance of dTMP-synthase as a target for drug development is discussed with respect to these findings.

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