A phase I dose escalation study of high-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous peripheral blood stem cell transplantation (PBSCT) in patients with solid tumors and hematologic malignancies


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Demirer T., Ilhan O., Mandel N., Arat M., Gunel N., Celebi H., ...Daha Fazla

BONE MARROW TRANSPLANTATION, cilt.25, sa.7, ss.697-703, 2000 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 25 Sayı: 7
  • Basım Tarihi: 2000
  • Doi Numarası: 10.1038/sj.bmt.1702239
  • Dergi Adı: BONE MARROW TRANSPLANTATION
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.697-703
  • Gazi Üniversitesi Adresli: Hayır

Özet

The purpose of this study was to determine the maximum tolerated dose of carboplatin administered with 500 mg/m(2) thiotepa and 100 mg/m(2) melphalan followed by autologous peripheral blood stem cell (PBSC) infusion in patients with refractory malignancies. Twenty-eight patients with refractory malignancies received high-dose thiotepa (500 mg/m(2), melphalan (100 mg/m(2)) and escalating doses of carboplatin 900-1500 mg/m(2)) followed by infusion of cryopreserved autologous PBSCs, The maximum tolerated doses were determined to be 500 mg/m(2) thiotepa, 100 mg/m(2) melphalan and 1350 mg/m(2) carboplatin. Two consecutive patients receiving 1500 mg/m(2) carboplatin experienced grade 3 mucositis and colitis, Ten patients were enrolled at the maximum tolerated dose and none had grade 3-4 regimen-related toxicity and mortality. All patients at this level experienced grade 1-2 mucositis, 90% grade 1-2 gastrointestinal toxicity, 30% grade 1-2 cardiac and renal toxicity, and 10% experienced grade 1 hepatic toxicity, The median time to achieve a granulocyte count of 0.5 x 10(9)/l was 9 days (range 7-12 days) and platelet count of 20 x 10(9)/l was 10 days (range 7-15 days), Of eight patients with stage IV refractory breast cancer, even were evaluable for response, one patient on day 75 will be evaluated soon. Five of seven (71.5%) evaluable patients achieved a complete remission (CR) and two had no response. Of seven patients with non-Hodgkin's lymphoma (n = 4) or Hodgkin's disease (n = 3), five achieved a CR (71.5%). Thiotepa, melphalan and carboplatin can be administered in high doses with tolerable mucositis as the major side-effect. This combination has significant activity in patients with breast cancer, and phase II studies in patients with breast cancer and other chemotherapy-sensitive malignancies are warranted.