title: Melphalan: a promising agent in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
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.
authors.affiliation: Institute for Cancer Care, Mercy Medical Center, Baltimore, MD, USA, asardi@mdmercy.com.
authors.forename: Armando
authors.initials: A
authors.lastname: Sardi
authors.forename: William
authors.initials: W
authors.lastname: Jimenez
authors.forename: Carol
authors.initials: C
authors.lastname: Nieroda
authors.forename: Michelle
authors.initials: M
authors.lastname: Sittig
authors.forename: Suven
authors.initials: S
authors.lastname: Shankar
authors.forename: Vadim
authors.initials: V
authors.lastname: Gushchin
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D010478:Chemotherapy, Cancer, Regional Perfusion; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D008558:Melphalan / Q000627:therapeutic use*; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D010534:Peritoneal Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan