Abstract P1-06-06: Oral cyclophosphamide-induced hemorrhagic cystitis from metronomic Cyclophosphamide/Methotrexate/5-Fluorouracil for treatment of synchronous bilateral breast cancer – A case report

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Abstract Introduction: Cyclophosphamide/methotrexate/5-fluororuracil (CMF) has been used for the treatment of early-stage breast cancer since the 1970s. Cyclophosphamide, a main component of the CMF regimen, is an alkylating agent with potential to cause hemorrhagic cystitis. This side effect is thought to be dose-dependent, with incidence up to 12-41% reported with doses of 150 – 200 grams. The risk of cyclophosphamide-induced hemorrhagic cystitis is very low with CMF, due to the low dose used in this regimen. At these doses of oral cyclophosphamide in CMF, intravenous (IV) hyperhydration or supportive care with mesna is not recommended. At the Fred Hutchinson Cancer Center, metronomic CMF (mCMF) is utilized in the adjuvant setting, where smaller doses are administered weekly for patients who may not tolerate higher doses of chemotherapy in traditional CMF. Cho and colleagues demonstrated similar efficacy and more tolerable side effect profile when compared with traditional CMF as well. The following report presents a patient with cyclophosphamide-induced hemorrhagic cystitis while receiving therapy with mCMF for the treatment of her breast cancer. Case Report: In April 2021, a 46-year-old female was diagnosed with cT2 cN0 cM0 estrogen receptor (ER)-/ progesterone receptor (PR)-positive, human epidermal growth factor receptor (HER)2-negative IDC of the right breast in addition to cT1b cN0 cM0 ER-positive, PR-negative, HER2-negative IDC of the left breast. Her past medical history included ulcerative colitis status post ileostomy, history of Stevens-Johnson syndrome with sulfa drugs, and mucinous cystadenoma of the ovary status post total abdominal hysterectomy and bilateral salpingo-oophorectomy. In June 2021, the patient presented to the Fred Hutchinson Cancer Center for initiation of adjuvant systemic therapy with mCMF. Her regimen consisted of cyclophosphamide 60 mg/m2 by mouth once daily, methotrexate 15 mg/m2 given intravenously once weekly, and 5-fluorouracil 300 mg/m2 given intravenously once weekly. She began treatment in July 2021, and her total dose of oral cyclophosphamide was 125 mg daily. Prior to week 11 of treatment, the patient reported persistent dysuria, urinary urgency, and hematuria. Despite several emergency department visits, antibiotic usage, and non-pharmacologic supportive care, she continued to have urinary symptoms. Ultimately, she was diagnosed with cyclophosphamide-induced hemorrhagic cystitis, confirmed by cystoscopy and cytopathology. The cyclophosphamide was discontinued at this time and the patient had received a total of 9.4 grams of oral cyclophosphamide over a 75-day period. With the resolution of her cystitis, adjuvant chemotherapy with only methotrexate and 5-fluorouracil was resumed 37 days after her last methotrexate and 5-fluouracil infusions and 30 days after her last dose of oral cyclophosphamide. Discussion: To date, there are four case reports of cyclophosphamide-induced hemorrhagic cystitis in patients with breast cancer. Two patients received capecitabine and oral cyclophosphamide while two patients received docetaxel and intravenous cyclophosphamide, all receiving cyclophosphamide at higher doses than the patient described in this case report. This case is the first to describe cyclophosphamide-induced hemorrhagic cystitis with adjuvant mCMF with oral cyclophosphamide at the lower dose of 60 mg/m2. The exact etiology of this adverse effect in this patient remains unclear; some hypothesized patient risk factors include reported nightly administration technique and her history of ulcerative colitis requiring ileostomy leading to inadequate oral hydration and bladder voiding and reduced fluid absorption, respectively. Citation Format: Jina Yun, Grace Baek, Arianne Duong, Dane Fritzsche, William Gwin. Oral cyclophosphamide-induced hemorrhagic cystitis from metronomic Cyclophosphamide/Methotrexate/5-Fluorouracil for treatment of synchronous bilateral breast cancer – A case report [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-06-06.

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