Hemorrhagic cystitis in a patient without a past history of radiation therapy who was treated with cabazitaxel for CRPC

Abstract

We report a case of cabazitaxel (CBZ)-induced hemorrhagic cystitis in a patient with metastatic castration-resistant prostate cancer (CRPC) progressing after docetaxel. The patient had not a past history of pelvic radiation therapy. A 62-year-old man was diagnosed with metastatic prostate cancer, Gleason score 5 + 4, in May 2013. PSA concentration was 92 ng/ml. MRI showed a prostatic tumor invading the bladder and multiple metastases to pelvic lymph nodes. Based on the results, the patient underwent combined androgen blockade therapy. His serum PSA level decreased to 5 ng/ml, but gradually increased thereafter and he was diagnosed with CRPC. When the PSA level reached 11.4 ng/ml in October 2013, he presented to our hospital and was started on docetaxel 75 mg/m2 every 3 weeks cycle in November 2013. After 11 cycles of docetaxel chemotherapy, PSA decreased to 4.57 ng/ml; however, MRI indicated residual tumor at the prostate invading the bladder. Pathological examination by transurethral biopsy (TURB) revealed residual and viable poorly differentiated prostatic adenocarcinomas. Therefore, we diagnosed him as having docetaxel-resistant CRPC and the patient was started on CBZ 25 mg/m2 according to protocol in October 2014. In Japan, CBZ was approved in September 2014 [1.Nozawa M. Mukai H. Takahashi S. et al.Japanese phase I study of cabazitaxel in metastatic castration-resistant prostate cancer.Int J Clin Oncol. 2015; 20: 1026-1034Crossref PubMed Scopus (36) Google Scholar]. After three cycles of CBZ chemotherapy, PSA decreased to 0.13 ng/ml; however, he presented to our hospital with gross hematuria. Cystoscopy revealed inflammatory and hemorrhagic mucosa from the neck to the top wall of the bladder without obvious nodal lesions (Figure 1A). Urine cytology and urine culture were negative in the study. Neither blood test result nor skin disorder related to an allergic action was developed. Bladder irrigation was not needed. Discontinuation of CBZ resulted in the cessation of gross hematuria and symptom of cystitis (Figure 1B). MRI indicated that the tumors disappeared after CBZ chemotherapy. Therefore, we suspected that the gross hematuria was a CBZ-induced hemorrhagic cystitis. The follow-up observation is still ongoing. To our knowledge, this is the first case of CBZ-induced hemorrhagic cystitis in a patient with metastatic CRPC and without a history of radiation therapy. Hemorrhagic cystitis has been associated with cyclophosphamide-induced or radiation-induced adverse events [2.Burris III, H.A. Hurtig J. Radiation recall with anticancer agents.Oncologist. 2010; 15: 1227-1237Crossref PubMed Scopus (193) Google Scholar]. Hemorrhagic cystitis in patients previously subjected to pelvic radiation therapy was named as radiation recall syndrome induced by CBZ [3.Grellety T. Houede N. Hoepffner J.L. et al.Hemorrhagic cystitis in patients treated with cabazitaxel: a radiation recall syndrome?.Ann Oncol. 2014; 25: 1248-1249Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar]. In previous case series, differential diagnosis of hematuria induced by disease progression was eliminated by TURB. In our patient, this adverse event was an unexpected reaction to CBZ. The mechanism of this reaction to CBZ is not known as yet. Seventeen percent hematuria of all grades was found in the CBZ arm of the TROPIC, and the metabolism of CBZ, which occurs mainly in the liver, does not provide an explanation for the occurrence of hemorrhagic cystitis [4.de Bono J.S. Oudard S. Ozguroglu M. et al.Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial.Lancet. 2010; 376: 1147-1154Abstract Full Text Full Text PDF PubMed Scopus (2624) Google Scholar]. During gross hematuria, he had no coagulation disorder or liver dysfunction. Adverse reaction report was performed by the manufacturer to the Pharmaceuticals and Medical Devices Agency in Japan. Our case may guide management of patients with gross hematuria after the treatments with CBZ and suggests the importance of urological investigation with drug withdrawal. The authors have declared no conflicts of interest.