Double dose-intensive chemotherapy with autologous stem cell support for relapsed and refractory testicular cancer : the University of Michigan experience and literature review

• Published in: Bone marrow transplantation (Basingstoke) Vol. 27; no. 9; pp. 939 - 947
• Main Authors: AYASH, L. J, CLARKE, M, SILVER, S. M, BRAUN, T, UBERTI, J, RATANATHARATHORN, V, REYNOLDS, C, FERRARA, J, BROUN, E. R, ADAMS, P. T
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.05.2001
• Subjects: Adolescent; Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - toxicity; Autografts; Biological and medical sciences; Bone marrow; Bone marrow transplantation; Bone Marrow Transplantation - mortality; Cancer; Carboplatin; Carboplatin - administration & dosage; Carboplatin - toxicity; Chemotherapy; Cisplatin; Cohort Studies; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Disease-Free Survival; Etoposide; Etoposide - administration & dosage; Etoposide - toxicity; Hematopoietic Stem Cell Transplantation - mortality; Humans; Literature reviews; Male; Medical prognosis; Medical sciences; Middle Aged; Neoplasms, Germ Cell and Embryonal - mortality; Neoplasms, Germ Cell and Embryonal - therapy; Patients; Pharmacology. Drug treatments; Platinum; Recurrence; Salvage Therapy; Seminoma; Stem cell transplantation; Stem cells; Testes; Testicular cancer; Testicular Neoplasms - mortality; Testicular Neoplasms - therapy; Transplantation; Transplantation, Autologous - mortality; Transplants; Transplants & implants; Treatment Outcome; Antineoplastic agent; Relapse; Stem cell; Hematopoietic cell; Testicle; Autograft; Isomerases; Phase II trial; Graft; Male genital diseases; High dose; Platinum II Complexes; Human; DNA topoisomerase (ATP-hydrolysing); Drug combination; Enzyme; Etoposide; Enzyme inhibitor; Malignant tumor; Podophyllotoxine derivatives; Resistance; Chemotherapy; Treatment; Carboplatin; Phase I trial; Testicular diseases; Bibliographic review
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1703008

Testicular cancer patients refractory or in relapse after primary chemotherapy have < or =25% 5-year progression-free survival with salvage. To improve prognosis, patients entered a phase I/II tandem dose-escalation trial of carboplatin (1500-2100 mg/m(2)) and etoposide (1200-2250 mg/m(2)) with ABMT. Patients were eligible for a second cycle if disease progression was absent and performance status allowed. From August 1990 to June 1998, 29 males (25 NSGCT) were treated. At the time of ABMT, 10 were chemosensitive, four were chemoresistant, and 10 were absolutely refractory to platinum. Disease status (no. patients) at transplant: primary refractory disease (six), first relapse (10), second relapse (eight), third relapse (five). Fifteen (52%) received both transplants. Treatment-related mortality was 10%. Best response after ABMT included: two CR, one CR surgically NED, five PR, three PR surgically NED, seven SD, and eight PD. Eight (28%) patients are continuously progression-free a median 60 months (range, 31-93) from first ABMT. Three seminoma patients remain progression-free. Of five long-term NSGCT survivors, four were treated in first relapse with platinum-sensitive disease. Eighteen relapses occurred a median of 4 months after ABMT I (two late relapses at 28 and 44 months). The median PFS and OS for the whole group are 4 and 14 months, respectively. Patients with relapsed/ refractory testicular cancer benefit most from ABMT if they have platinum-sensitive disease in first relapse. Patients who do poorly despite ABMT have a mediastinal primary site, true cisplatin-refractory disease, disease progression prior to ABMT, and/or markedly elevated betaHCG at ABMT. New treatment modalities are needed for the latter group.