Metronomic therapy in metastatic castrate-resistant prostate cancer: Experience from a tertiary cancer care center

Indian J Cancer. 2018 Jan-Mar;55(1):94-97. doi: 10.4103/ijc.IJC_346_17.

Abstract

Background: Many agents have shown survival advantage in metastatic castrate-resistant prostate cancer (mCRPC). Despite this improvement, survival is poor, especially in subgroup of elderly patients who are not fit for cytotoxic chemotherapy.

Materials and methods: This is a single-institutional data review of mCRPC treated between December 2012 and May 2016 with oral cyclophosphamide (50-100 mg/day) ± oral prednisolone. mCRPCs failed or not fit for docetaxel and/or abiraterone were included in this study. Monthly prostate-specific antigen (PSA) was monitored, and toxicity of cyclophosphamide was recorded. PSA response was defined as ≥50% reduction from precyclophosphamide value. The median follow-up was calculated from the day of starting cyclophosphamide and the last date of follow-up or death, whichever is later.

Results: Eighteen patients were included with a median age of 74.5 years (range: 59-83). The site of metastasis was bone in 15, bone and distant lymph nodes in 2, and rectum in 1 patient. The median duration of androgen deprivation was 21 months (range: 3-42.9 months). The median cyclophosphamide exposure was 2 months (range: 0.9-13.5 months) after a median follow-up of 5.8 months. Overall PSA response rate was 44%. The median PSA progression-free survival with cyclophosphamide was 4.7 months (range: 0.9-13.5 months). Five patients had durable PSA response of 9.9, 10.1, 10.5, 12.1, and 13.5 months, respectively. No Grade 3 or 4 toxicity was observed with cyclophosphamide.

Conclusion: Oral metronomic cyclophosphamide was found to be an effective and well-tolerated therapy in mCRPC after failure or not fit for docetaxel and/or abiraterone. In few patients, cyclophosphamide induced durable PSA response. This finding needs further evaluation in a prospective manner.

Keywords: Cyclophosphamide; metastatic; prostate; steroids.

MeSH terms

  • Administration, Metronomic*
  • Aged
  • Aged, 80 and over
  • Androstenes / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols
  • Cyclophosphamide / administration & dosage*
  • Cyclophosphamide / adverse effects
  • Disease-Free Survival
  • Docetaxel
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / blood
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / epidemiology
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Taxoids / administration & dosage
  • Tertiary Care Centers
  • Treatment Outcome

Substances

  • Androstenes
  • Taxoids
  • Docetaxel
  • Cyclophosphamide
  • Prostate-Specific Antigen
  • abiraterone