title: [Chemo-/immunotherapy in advanced malignant melanoma: carboplatin and DTIC or cisplatin, dtic, bcnu and tamoxifen followed by immunotherapy with interleukin 2 and interferon alpha-2a].
abstract: BACKGROUND
  Polychemotherapy and immunomodulating treatment using IL-2 and/or IFN-alpha produce objective responses in a proportion of advanced malignant melanoma patients.
  
  
  METHODS
  In 2 consecutive phase II trials in a total of 85 patients, we assessed the potential synergism between both modalities i.e., chemo- and immunotherapy. Treatment consisted of intravenous carboplatin (CBDCA, 400 mg/m2) and dacarbazine (DTIC, 750 mg/m2) given twice at a 3-week interval, or 4 cycles of DTIC (220 mg/m2 i.v. x 3 days), cisplatin (DDP 35 mg/m2 i.v. x 3 days), carmustine (BCNU 150 mg/m2 i.v., cycles 1 and 3) and tamoxifen (TAM 20 mg/per os x 5 days) at a 3-week interval. Chemotherapy was followed by immunotherapy with combined subcutaneous interleukin-2 and (rIL-2) and s.c. interferon-alpha 2a (rIFN-alpha).
  
  
  RESULTS
  Among 40 patients who received a full cycle of chemotherapy with CBDCA/DTIC and sequential immunotherapy, there were 3 (7.5%) complete remissions (CR) with durations of 13 to 26+ months. Partial remissions (PR) were noted in 11 (27.5%) patients with a median response duration of 8 (range 5 to 14) months. Among 45 patients who received DTIC/DDC/DDP/BCNU and TAM and sequential rIL-2/rIFN-alpha 2a there were 5 (11%) complete remissions and 17 (38%) partial remissions. Duration of complete and partial remissions ranged from 8+ to 24+ months (median 12+) and 5+ to 17 months (median 8+), respectively. Chemotherapy produced mostly moderate toxicity. Thrombocytopenia was common with the nadir after a median time of 17 days following start of the chemotherapy. 19 patients required transfusion of thrombocytes. Nausea and vomiting due to chemotherapy were well tolerated using concomitant ondansetrone (8 mg i.v.). Immunotherapy was self-administered at home with mild to moderate side-effects; malaise, fever, chills, nausea/vomiting, diarrhea, anorexia and arthralgias were most frequent (70% to 100%), but spontaneously reversible after ending the immunotherapy. A mean of 87% (trial I) to 89% (trial II) of the projected doses of rIL-2 and rIFN-alpha were administered on either protocol. There were no life-threatening complications and no treatment-related deaths.
  
  
  CONCLUSIONS
  The sequential combination of chemotherapy and immunotherapy had at least additive therapeutic activity against metastatic malignant melanoma. Both schedules produced long-lasting remissions and were overall well tolerated. These trials substantiate a potential role for low to intermediate dose immunotherapy in maintaining and consolidating therapeutic effects of chemotherapy in metastatic melanoma.
authors.affiliation: Klinik für Hämatologie und Onkologie, Städtisches Krankenhaus Siloah, Hannover.
authors.forename: H H
authors.initials: HH
authors.lastname: Kirchner
authors.forename: J
authors.initials: J
authors.lastname: Atzpodien
authors.forename: H
authors.initials: H
authors.lastname: Poliwoda
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012878:Skin Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D013629:Tamoxifen; D003606:Dacarbazine; D016190:Carboplatin; D002945:Cisplatin; D002330:Carmustine
vernacular_title: Chemo-/Immuntherapie beim fortgeschrittenen malignen Melanom: Carboplatin und DTIC oder Cisplatin, DTIC, BCNU und Tamoxifen und anschliessende Immuntherapie mit Interleukin-2 und Interferon-alpha2a.