title: Retrolective cohort study of an additive therapy with an oral enzyme preparation in patients with multiple myeloma.
abstract: OBJECTIVE
  To evaluate the impact of an additive therapy with an oral enzyme (OE) preparation given for more than 6 months additionally to standard combination chemotherapy (vincristine/melphalan/cyclophosphamide/prednisone (VMCP)- or methylprednisolone/ vincristine/CCNU/cyclophosphamide/melphalan (MOCCA)-regimen) in the primary treatment of patients with multiple myeloma stages I-III.
  
  
  METHODS
  A cohort of 265 patients with multiple myeloma stages I-III was consecutively treated at our institution in two parallel groups (control group (n = 99): chemotherapy +/-OE for less than 6 months; OE-group (n = 166): chemotherapy + OE for more than 6 months). The median follow-up time in the stages I, II, and III for the OE-group was 61, 37, and 46.5 months, respectively; for the control group the respective values were 33, 51.5, and 31.5 months. The primary endpoint of the study was disease-specific survival. Secondary endpoints were response to therapy, duration of first response and side effects. The chosen method for evaluation was the technique of a retrolective cohort analysis with a concurrent control group. Survival analysis was performed by the Kaplan-Meier method and multivariate analysis was done with the Cox proportional hazards model.
  
  
  RESULTS
  Significantly higher overall response rates and longer duration of remissions were observed in the OE-group. Primary responders showed a longer mean survival time than non-responders. Additive therapy with OE given for more than 6 months decreased the hazard of death for patients at all stages of disease by approximately 60%. Observation time was not long enough to estimate the median survival for patients at stages I and II; for stage III patients it was 47 months in the control group versus 83 months for the patients treated with OE (P = 0.0014) which means a 3-year gain of survival time. Significant prognostic factors for survival, in the Cox regression analysis, were stage of disease and therapy with OE. The OE-therapy was generally well tolerated (3.6% of patients with mild to moderate gastrointestinal symptoms).
  
  
  CONCLUSIONS
  OEs represent a promising new additive therapy in multiple myeloma which will be further evaluated in a randomized phase III trial in the USA.
authors.affiliation: Clinic of Haematology and Transfusion Medicine, University of Brastislava, Slovak Republic.
authors.forename: A
authors.initials: A
authors.lastname: Sakalová
authors.forename: P R
authors.initials: PR
authors.lastname: Bock
authors.forename: L
authors.initials: L
authors.lastname: Dedík
authors.forename: J
authors.initials: J
authors.lastname: Hanisch
authors.forename: W
authors.initials: W
authors.lastname: Schiess
authors.forename: S
authors.initials: S
authors.lastname: Gazová
authors.forename: I
authors.initials: I
authors.lastname: Chabronová
authors.forename: D
authors.initials: D
authors.lastname: Holomanova
authors.forename: M
authors.initials: M
authors.lastname: Mistrík
authors.forename: M
authors.initials: M
authors.lastname: Hrubisko
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002918:Chymotrypsin / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004338:Drug Combinations; D010450:Endopeptidases / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D010206:Papain / Q000008:administration & dosage* / Q000009:adverse effects; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate; D014357:Trypsin / Q000008:administration & dosage* / Q000009:adverse effects; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D004338:Drug Combinations; D014750:Vincristine; C009685:chymotrypsin, papain, trypsin drug combination; D008130:Lomustine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D010450:Endopeptidases; D002918:Chymotrypsin; D014357:Trypsin; D010206:Papain; D008558:Melphalan; D011241:Prednisone; D008775:Methylprednisolone