Cyclophosphamide in Treatment of Disseminated Malignant Disease

Anders, C. J.; Kemp, N. H.

doi:10.1136/bmj.2.5266.1516

Cited by 32 publications

(5 citation statements)

References 7 publications

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“…The nitrogen mustard phosphamide ester, cyclophosphamide, is an alkylating agent that induces apoptosis in rapidly dividing cells, which usually leads to alopecia [1]. Chemotherapy-induced alopecia can cause much anguish among cancer patients; most report at least mild distress [2].…”

Section: Introductionmentioning

confidence: 99%

“…Anagen matrix keratinocytes are some of the most rapidly dividing cells in the body, with as many as 60% in S-phase [5]. By targeting dividing cells, chemotherapy-induced apoptosis causes aberrant and premature involution of the hair follicle in humans and animal models, although the process occurs more rapidly in the mouse [1], [6], [7]. Despite progress in identifying the histological changes of chemotherapy-induced alopecia, our understanding of its mechanisms has limited the development of strategies to alleviate it.…”

Section: Introductionmentioning

confidence: 99%

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Role for the Epidermal Growth Factor Receptor in Chemotherapy-Induced Alopecia

et al. 2013

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Treatment of cancer patients with chemotherapeutics like cyclophosphamide often causes alopecia as a result of premature and aberrant catagen. Because the epidermal growth factor receptor (EGFR) signals anagen hair follicles to enter catagen, we hypothesized that EGFR signaling may be involved in cyclophosphamide-induced alopecia. To test this hypothesis, skin-targeted Egfr mutant mice were generated by crossing floxed Egfr and Keratin 14 promoter-driven Cre recombinase mice. Cyclophosphamide treatment of control mice resulted in alopecia while Egfr mutant skin was resistant to cyclophosphamide-induced alopecia. Egfr mutant skin entered catagen normally, as indicated by dermal papilla condensation and decreased follicular proliferation, but did not progress to telogen as did Egfr wild type follicles. Egfr mutant follicles responded with less proliferation, apoptosis, and fewer p53-positive cells after cyclophosphamide. Treatment of control mice with the EGFR inhibitors erlotinib or gefitinib similarly suppressed alopecia and catagen progression by cyclophosphamide. Secondary analysis of clinical trials utilizing EGFR-targeted therapies and alopecia-inducing chemotherapy also revealed evidence for involvement of EGFR in chemotherapy-induced alopecia. Taken together, our results demonstrated the involvement of EGFR signaling in chemotherapy-induced alopecia, which will help in the design of novel therapeutic regimens to minimize chemotherapy-induced alopecia.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role for the Epidermal Growth Factor Receptor in Chemotherapy-Induced Alopecia

et al. 2013

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“…In a series of 92 patients treated with cyclophosphamide by Anders and Kemp (1961), alopecia occurred in 60 % and was complete in 25 %. Normal regrowth of hair , however, cannot be guaranteed , and the patient should be warned.…”

Section: Alopeciamentioning

confidence: 99%

Antineoplastic and Immunosuppressive Drugs1 III

Cridland

1972

Drugs

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“…The drug acts by binding an alkyl group to the Guanine base of DNA, thus producing irreversible crosslinkages in the DNA strands that leads to cell death in the G2-and S-phases of the cell cycle. Due to this cytotoxic property, it is used extensively in a variety of carcinomas, either as monotherapy or in combination with other drugs [5]. CYP is also used at lower doses for some autoimmune diseases, such as systemic lupus erythematosus, severe rheumatoid arthritis, multiple sclerosis, glomerulonephritis, and post organ transplantation for prevention of organ rejection [6].…”

Section: Introductionmentioning

confidence: 99%

Effect of Cyclophosphamide and Its Combination with Metformin on the Survival Rate in Mice

Alhowail

Sajid

Almogbel

et al. 2019

JPRI

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Background: Cyclophosphamide (CYP), an alkylating chemotherapeutic agent, is widely used to treat several types of cancer. Its toxic effects are well-established and include hepatotoxicity, nephrotoxicity, and bone marrow suppression. Metformin (MET) is an anti-diabetic medication that is considered a first-line therapy for type 2 diabetes mellitus. In this study, we aimed to investigate the effect of co-administration of MET on CYP-induced toxicity by recording the survival rate in mice. Methods: Fifty mice (body weight 30-35 gm) were divided into four groups as control and treatments and comprised of 12-13 animals of either sex. The animals in the control group received 4 doses of saline by injection. The animals in the CYP group received 4 doses of CYP (100 mg/kg) (intraperitoneal). The animals in the MET group received lower daily dose (30 mg/kg) in drinking water (3 mg/ml), starting 3 days prior to CYP injection and lasting until the final injection of CYP. Alhowail et al.; JPRI, 30(2): 1-6, 2019; Article no.JPRI.51861 2 Original Research ArticleThe animals in the combination group (CYP and MET) received 4 doses of CYP (100 mg/kg) and a daily dose of MET in drinking water (3 mg/ml). The animals were observed daily to record the mortality and their body weights were recorded every alternate day. The data obtained from the study was statistically analyzed by one-way ANOVA, and p<0.05 was considered significant. Results: The data obtained from the study indicated that CYP administration increased the rate of mortality significantly (p < 0.01) when compared to the control animals, while MET reduced the rate. When the combination of CYP and MET was tested, the mortality rate was found to be increased. Both CYP and MET significantly reduced the body weight compared to the control animals. Conclusion: The results indicated that the combination of CYP and MET reduced the survival rate of animals, suggesting that although MET possesses anti-proliferative action, it has the potential to increase the toxic effects of CYP when combined with CYP.

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Cyclophosphamide in Treatment of Disseminated Malignant Disease

Cited by 32 publications

References 7 publications

Role for the Epidermal Growth Factor Receptor in Chemotherapy-Induced Alopecia

Role for the Epidermal Growth Factor Receptor in Chemotherapy-Induced Alopecia

Antineoplastic and Immunosuppressive Drugs1 III

Effect of Cyclophosphamide and Its Combination with Metformin on the Survival Rate in Mice

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