Cyclophosphamide treatment of systemic lupus erythematosus: risk of bladder cancer exceeds benefit.

Elliott, R.; Essenhigh, D. M.; Morley, A. R.

doi:10.1136/bmj.284.6323.1160

Cited by 53 publications

(18 citation statements)

References 2 publications

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“…Previous reports have suggested a possible role of cyclophosphamide in inducing malignant transformation (17). The present data and those reported by Petterson et a1 (9) indicate that the occurrence of NHL and other hematopoietic cancers is not related to the use of cyclophosphamide.…”

Section: Discussionsupporting

confidence: 76%

Malignancy in systemic lupus erythematosus

Abu‐Shakra

Gladman

Urowitz

1996

Arthritis & Rheumatism

163

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Objective. To estimate the risk of cancer in patients with systemic lupus erythematosus (SLE).Methods. Patients with SLE (n = 724) have been followed prospectively, for 24 years, at the University of Toronto Lupus Clinic. The diagnosis of cancer was confirmed by histologic or autopsy reports. Standardized rates of cancer and standardized incidence rates (SIR) (ratio of observed-to-expected cancers) were used to estimate the risk for cancers.Results. Twenty-four cancers were identified in 23 SLE patients (3.2%) during 7,233 patient-years of followup. Compared with the Ontario population, the overall estimated risk for all cancers was not increased in the lupus cohort (SIR 1.08, 95% confidence interval 0.70-1.62). A 4

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Section: Discussionsupporting

confidence: 76%

Malignancy in systemic lupus erythematosus

Abu‐Shakra

Gladman

Urowitz

1996

Arthritis & Rheumatism

163

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“…Although increased cancer rates among SLE patients (particularly with respect to lymphomas and leukemias) have been linked to treatment with immunosuppressive agents such as cyclophosphamide, azathioprine, and methotrexate [47][48][49][50], we were not able to examine this association, as we did not have treatment information on the patients. Several case series have supported the contention that there is an increased risk of bladder cancer among SLE patients because many of them are treated with cyclophosphamide [51][52][53]. Surprisingly, the SIR for bladder cancer in our cohort was not significantly increased.…”

Section: Discussionmentioning

confidence: 50%

Cancer risk in a cohort of patients with systemic lupus erythematosus (SLE) in California

Parikh‐Patel

White

Allen

et al. 2008

Cancer Causes Control

128

153

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Objective-We conducted a retrospective cohort study to examine cancer risk in a large cohort of systemic lupus erythematosus (SLE) patients in California.Methods-The cohort consisted of individuals with SLE derived from statewide patient discharge data during the period 1991-2002. SLE patients were followed using cancer registry data to examine patterns of cancer development. Standardized incidence ratios (SlRs) and 95% CI were calculated to compare the observed to expected numbers of cancers based on age-, race-, and sex-specific incidence rates in the California population.Results-The 30,478 SLE patients were observed for 157,969 person-years. A total of 1,273 cancers occurred within the observation interval. Overall cancer risk was significantly elevated (SIR=1.14, 95% CI=1.07-1.20). SLE patients had higher risks of vagina/vulva (SIR=3.27, 95% CI=2.41-4.31) and liver cancers (SIR=2.70, 95% CI=1.54-4.24). Elevated risks of lung, kidney, and thyroid cancers and several hematopoietic malignancies were also observed. Individuals had significantly lower risks of several screenable cancers, including breast, cervix, and prostate.Conclusions-These data suggest that risks of several cancer types are elevated among SLE patients. Detailed studies of endogenous and exogenous factors that drive these associations are needed.The final publication is available at Sprinter via: http://dx

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“…In humans there is also strong evidence that it is a carcinogen (Plotz et al, 1979;Elliot et al, 1982), producing tumours of the bladder and possibly other sites.…”

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confidence: 99%

Risk of leukaemia in ovarian tumour and breast cancer patients following treatment by cyclophosphamide

Haas¹,

B²,

Wh³

et al. 1987

Br J Cancer

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Summary A case-control study was conducted to determine whether the development of leukaemia was associated with chemotherapy for neoplasms of the ovary or breast, in a population where most such chemotherapy consisted of cyclophosphamide alone. Cases and controls were identified from the National Cancer Registry of the German Democratic Republic. Cases were women who had developed leukaemia as a second primary after an initial diagnosis, at least one year before, of an ovarian or breast tumour. Controls were patients with an ovarian tumour or breast cancer who had survived to the year when the case developed a leukaemia but who had not themselves developed a second malignancy. Controls were matched to cases by the site of the first primary and its year of diagnosis, as well as year of birth. The relative risk for acute leukaemia following treatment with cyclophosphamide alone was significantly elevated (P<0.05), at 14.6 for ovarian tumour patients and 2.7 for breast cancer patients. Among breast cancer patients the increased risk of leukaemia associated with chemotherapy was confined to women who had been under 50 years of age at the time of diagnosis of the breast cancer (for whom the relative risk was 13.1). No excess risk of leukaemia was observed in association with radiotherapy for either ovarian or breast cancer patients. The present findings strongly suggest that cyclophosphamide as a single chemotherapeutic agent is capable of inducing leukaemia in humans.Cyclophosphamide is carcinogenic by several routes of administration in rats and mice (Schmahl & Habs, 1979; IARC, 1981). In humans there is also strong evidence that it is a carcinogen (Plotz et al., 1979;Elliot et al., 1982), producing tumours of the bladder and possibly other sites.There are a number of case reports of acute leukaemia following treatment with cyclophosphamide of nonmalignant diseases including rheumatoid arthritis, Wegener's granulomatosis, chronic glomerulonephritis, idiopathic thrombocytopaenia purpura, and Sj6gren's syndrome (Grunwald & Rosner, 1979). While cyclophosphamide is suspected to be a leukaemogen, it is widely believed to be less potent than many other nitrogen mustard-derived alkylating agents, and it is recommended as a component of adjuvant therapy following surgery for breast cancer (National Institutes of Health, 1986).Studies of leukaemia in cancer patients treated with cyclophosphamide have been difficult to interpret, because it is often given in combination with other agents known to be leukaemogenic. Although an increase in the risk of acute non-lymphocytic leukaemia (ANLL) following Hodgkin's disease has been appreciated for some time (Brody et al., 1977) it has not been possible to implicate directly cyclophosphamide, even though it has been widely used in Hodgkin's disease therapy (Boivin & Hutchison, 1984). Acute leukaemia also occurs in excess in patients with nonHodgkin's lymphoma who have undergone chemotherapy including cyclophosphamide (Pedersen-Bjergaard et al., 1985). In a study of multiple myeloma...

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Cyclophosphamide treatment of systemic lupus erythematosus: risk of bladder cancer exceeds benefit.

Cited by 53 publications

References 2 publications

Malignancy in systemic lupus erythematosus

Malignancy in systemic lupus erythematosus

Cancer risk in a cohort of patients with systemic lupus erythematosus (SLE) in California

Risk of leukaemia in ovarian tumour and breast cancer patients following treatment by cyclophosphamide

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