Cyclophosphamide factors

Cyclophosphamide 600 mg/m2 IV, day 1 Methotrexate 40 mg/m2 IV, day 1 Fluorouracil 600 mg/m2 IV, days 1 and 8 Repeat cycles every 28 days for 6 cycles Dose-dense AC —> paclitaxel Doxorubicin 60 mg/m2 IV bolus, day 1 Cyclophosphamide 600 mg/m2 IV, day 1 Repeat cycles every 14 days for 4 cycles (must be given with growth factor support) Followed by ... 

Risk factors for the development of AML include exposure to environmental toxins, Hispanic ethnicity, and genetics.6 Of greater concern is the increased prevalence of AML as a secondary malignancy, resulting from chemotherapy and radiation treatment for other cancers. Alkylating agents, such as ifosfamide and cyclophosphamide, and topoisomerase inhibitors, such as etoposide, are linked to an increased risk of myelodysplastic syndrome (MDS) and AML.8... 

Levesque JP, Hendy J, Takamatsu Y, Williams B, Winkler IG, Simmons PJ. Mobilization by either cyclophosphamide or granulocyte colony-stimulating factor transforms the bone marrow into a highly proteolytic environment. Exp Hematol 2002 30(5) 440-449. 

Neutropenia is a condition characterized by a decrease in blood neutrophil count below 1.5 X 109 cells per litre a normal blood count is (2.0-7.5) X 109 cells per litre. Its clinical symptoms include the occurrence of frequent and usually serious infections, often requiring hospitalization. Neutropenia may be caused by a number of factors (Table 10.6), at least some of which are responsive to CSF treatment. Particularly noteworthy is neutropenia triggered by administration of chemotherapeutic drugs to cancer patients. Chemotherapeutic agents (e.g. cyclophosphamide, doxorubicin and methotrexate), when administered at therapeutically effective doses, often induce the destruction of stem cells and/or compromise stem cell differentiation. 

Doxorubicin 60 mg/m2 IV bolus, day I Cyclophosphamide 600 mj m2 IV, day I Repeat cycles every 14 days for four cycles (must be given with growth factor support)... 

Acquired factor XIII antibodies Cyclophosphamide plus factor XIII Usually good... 

Green D, Suppression of an antibody to factor VIII by a combination of factor VIII and cyclophosphamide, Blood 1971 37 381-387. 

Astralagus 2. Echinacea 3. Liquorice 4. Milk thistle 5. Neem 6. Sea buckthorn 1. Ciclosporin 2. Azathioprine 3. Methotrexate 4. Tacrolimus 5. Dadizumab 6. Cyclophosphamide Possibility of graft rejection 1 blood level unknown mechanism (astralagus). Other mechanisms alkyl amides from echinacea modulate tumour necrosis factor alpha mRNA expression in human monocytes/macrophages via the cannabinoid type 2 receptor Unknown mechanism (milk thistle is known to l cyclosporine levels neem L effects of azathioprine, prednisolone and dadizumab sea buckthorn may 1 effect of cyclophosphamide) Induces metabolizing enzymes, CYP3A4 and P-gp (St John s wort L ciclosporin and tacrolimus levels) Avoid concomitant use of the herb... 

A syndrome of palmar-plantar erythema (progressing in some patients to blistering and desquamation) has been reported in seven of eight patients with advanced breast or ovarian cancer who received high-dose doxorubicin (125-150 mg/m ) (79). By contrast, in a similar dose intensification study in which patients received epirubicin 200 mg/m with cyclophosphamide and growth factor support, the pal-mar-plantar syndrome did not occur (80). 

Susceptibihty factors have been investigated in a large retrospective study of 274 patients aged under 45 years, of whom 70 had received cyclophosphamide, 84 azathiopr-ine but not cyclophosphamide, and 88 either no drug or hydroxychloroquine alone (35). The overall incidence of ovarian failure, defined as sustained amenorrhea for at least 12 months and documented by reduced estradiol concentrations, was 26, 1, and 0% respectively. The mean delay to onset of the first missed menses was 4.4 months. A higher age at the start of treatment and cumulative dose were independent risk factors for cyclophosphamide-induced ovarian failure. The incidences were 14, 28, and 50% in patients aged under 30 years, 30-39 years, and over 40 years respectively, and 4, 26, 31, 70%... 

In addition to cyclophosphamide, this patient had several susceptibility factors for fatal infection, namely age (older than 50 years) and a low leukocyte nadir (2900 x 10 /1) after treatment with cyclophosphamide and prednisone. 

Although tumor induction has mostly been documented in patients treated for cancer, long-term cyclophosphamide treatment for non-neoplastic conditions can also increase the incidence of certain neoplasms. Whether this oncogenic effect is a consequence of drug-induced chromosomal aberrations rather than immunosuppression is unclear. An increased incidence of bladder cancers, skin cancers, and myeloproliferative disorders was found in a 20-year follow-up study of 119 patients with rheumatoid arthritis, and a high dose of cyclophosphamide (mean total dose of 80 g) was the main susceptibihty factor (47). 

Squamous cell carcinoma of the bladder has been reported 4 years after pulsed cyclophosphamide therapy (50). However, the authors noted that other susceptibility factors, such as bladder diverticula and human papilloma virus infection, occurred in the intervening period and they speculated on the cumulative risk. 

The risk of ovarian failure and infertility has been studied in 84 women with an underlying inflammatory disease receiving intravenous cyclophosphamide (65). The incidence of sustained amenorrhea was 22% and was independent of the underlying inflammatory disease. After treatment with cyclophosphamide following bone marrow transplantation, ovarian function can occasionally recover, resulting in a successful pregnancy up to 7 years after treatment (66). No specific factors correlated with recovery of normal ovarian function. However, recovery was rare if the patient had undergone concurrent total body irradiation (67). 

The FDA has classified cyclophosphamide as a pregnancy risk factor D drug it is teratogenic in animals, but population studies have not conclusively shown teratogenicity in humans. However, in a study of in utero first-trimester exposure to four doses of cyclophosphamide 20 mg/kg it was concluded that cyclophosphamide is a human teratogen, that there is a distinct embryopathic phenotype, and that there are serious doubts about the safety of cyclophosphamide in pregnancy (68). The congenital malformation rate has been estimated at 10-44% (69). 

Goldberg MA, Antin JH, Guinan EC, Rappeport JM. Cyclophosphamide cardiotoxicity an analysis of dosing as a risk factor. Blood 1986 68(5) 1114-18. 

Mok CC, Lau CS, Wong RW. Risk factors for ovarian failure in patients with systemic lupus erythematosus receiving cyclophosphamide therapy. Arthritis Rheum 1998 41(5) 831-7. 

Pryor BD, Bologna SG, Kahl LE. Risk factors for serious infection during treatment with cyclophosphamide and high-dose corticosteroids for systemic lupus erythematosus. Arthritis Rheum 1996 39(9) 1475-82. 

Acute febrile interstitial pneumonitis occurred within less than 48 hours after the second to fourth cycles of chemotherapy (doxorubicin, cyclophosphamide, bleomycin, methotrexate, plus methylprednisolone) in five patients with non-Hodgkin s lymphoma who were receiving prophylactic G-CSF n — 3) or GM-CSF (n = 2) (23). Lymphocytic alveolitis was confirmed in four of these patients and all three patients tested had an increased number of CD8+ T cells. Even though all the patients received high-dose methylprednisolone, two died as a result of diffuse and extensive interstitial pulmonary fibrosis, demonstrated at postmortem. Although both G-CSF and GM-CSF can cause acute pneumonitis in patients with cancers, it is still unknown to what extent hemopoietic growth factors are involved in this complication. 

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