Melphalan: A Promising Agent in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Ann Surg Oncol. 2014 Mar;21(3):908-14. doi: 10.1245/s10434-013-3407-6. Epub 2013 Nov 26.

Abstract

Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has become an option for peritoneal carcinomatosis (PC). Frequently, these patients have failed systemic chemotherapies and surgeries, including CRS/HIPEC with traditional regimens (mitomycin-C or platinum based). An alternative agent for failed or repeated CRS/HIPEC is unknown. We hypothesize that melphalan is an alternative agent in patients with PC from aggressive primaries, including recurrences following failed regional therapies.

Methods: A retrospective review of a prospective database of 247 patients revealed 25 patients (9 male and 16 female) who received intraperitoneal melphalan (50 mg/m(2)) in 31 CRS/HIPEC procedures, of which 19 were repeated. Primary malignancies included 17 appendiceal, one colorectal, two ovarian, two uterine sarcomas, two primary peritoneal and one mesentery sarcoma.

Results: PC index (PCI) was ≥20 in 76 % of patients (19/25). 88 % of patients (22/25) had complete cytoreduction. Seventeen patients were alive, with mean survival of 63.6 months, and eight patients are deceased. Overall survival (OS) for the entire group since diagnosis was 95.8, 84.5, 50.9, and 38.2 % at 1, 3, 5, and 10 years, respectively; OS since melphalan HIPEC was 89.4, 45, and 30 % at 1, 3, and 5 years, respectively; and OS in patients with appendiceal malignancies was 91.7, 48.1 and 32.1 % at 1, 3 and 5 years, respectively. There was no postoperative mortality. Grade III-IV morbidity was 23 % (7/31). Nine patents had neutropenia, controlled with filgrastim.

Conclusions: Melphalan is an efficacious alternative agent in patients undergoing CRS/HIPEC for aggressive and recurrent peritoneal surface malignancies. Its postoperative significant myelosuppression effect should be addressed.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Chemotherapy, Adjuvant
  • Chemotherapy, Cancer, Regional Perfusion*
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperthermia, Induced*
  • Male
  • Melphalan / therapeutic use*
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Peritoneal Neoplasms / mortality
  • Peritoneal Neoplasms / secondary
  • Peritoneal Neoplasms / therapy*
  • Prognosis
  • Prospective Studies
  • Retrospective Studies
  • Survival Rate

Substances

  • Antineoplastic Agents, Alkylating
  • Melphalan