Dose escalation study of high-dose carboplatin and etoposide with autologous bone marrow support in patients with recurrent and refractory germ cell tumors

E. R. Broun, C. R. Nichols, R. Mandanas, D. Salzman, M. Turns, R. Hromas, Kenneth Cornetta, Lawrence Einhorn

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Thirty-three patients with germ cell cancer (GCT) recurrent after two cisplatin-based regimens or cisplatin refractory (progression within 4 weeks of the last dose of cisplatin) were enrolled in a trial to establish the maximum tolerated doses (MTD) of carboplatin and etoposide given in combination with ABMT for two cycles. BM harvest of ≥ 2 x 108 nucleated cells/kg preceded two cycles of therapy. Each agent was dose escalated, carboplatin from 1650 mg/m2 to 2100 mg/m2 and etoposide from 1200 mg/m2 to 2250 mg/m2 per cycle in successive cohorts. Twenty patients completed two cycles, 13 underwent only one due to: early death (4), toxicity (2), and progressive disease (6). There were four CR, three of whom achieved NED status with surgery, 14 PR, of whom eight have progressed. Four patients with stable disease and seven PD have died with a median survival of 6 months. There were six treatment-related deaths, four on course 1 and two on course 2. Causes of death on course 1 were: CNS hemorrhage (1), multiorgan failure (3); and on course 2: sepsis (1) and sudden death (1). Severe but reversible mucositis, transaminase and creatinine elevations were observed at the highest dose level. Three of five patients treated at this dose level had severe neurologic toxicity, manifested by both peripheral neuropathy and ototoxicity. The MTD in this patient population was carboplatin 2100 mg/m2 and etoposide 2250 mg/m2 on each of two cycles of therapy. Neurologic and mucosal toxicity were dose limiting.

Original languageEnglish (US)
Pages (from-to)353-358
Number of pages6
JournalBone Marrow Transplantation
Volume16
Issue number3
StatePublished - 1995
Externally publishedYes

Fingerprint

Germ Cell and Embryonal Neoplasms
Carboplatin
Etoposide
Bone Marrow
Cisplatin
Maximum Tolerated Dose
Nervous System
Mucositis
Peripheral Nervous System Diseases
Sudden Death
Transaminases
Cause of Death
Creatinine
Sepsis
Therapeutics
Hemorrhage
Survival
Population

Keywords

  • Bone marrow transplant
  • Carboplatin
  • Etoposide
  • Germ cell tumor

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Dose escalation study of high-dose carboplatin and etoposide with autologous bone marrow support in patients with recurrent and refractory germ cell tumors. / Broun, E. R.; Nichols, C. R.; Mandanas, R.; Salzman, D.; Turns, M.; Hromas, R.; Cornetta, Kenneth; Einhorn, Lawrence.

In: Bone Marrow Transplantation, Vol. 16, No. 3, 1995, p. 353-358.

Research output: Contribution to journalArticle

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