Observational studyTesticular cancer

High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors

N Engl J Med · 2007184 patients

Einhorn LH, Williams SD, Chamness A, Brames MJ, Perkins SM, Abonour R. N Engl J Med. 2007. 357:340-348

Study type: Observational study
Design: Retrospective review of consecutive patients at a single centre (Indiana University)
Sample size: 184 patients
Source: N Engl J Med · 2007

In plain words

In this study, men whose testicular cancer had come back or progressed after standard chemotherapy received very high-dose chemotherapy, after which their own blood-forming stem cells were given back to them. More than half of the patients stayed free of disease, even some whose cancer had not responded to standard chemotherapy. Serious side effects also occurred.

Key results

116 of 184

Complete remission without relapse (all patients)

Median follow-up 48 months (14 to 118 months)

94 of 135

Disease-free, treated in the second line

22 of 49

Disease-free, treated in the third line or later

18 of 40

Disease-free, refractory to standard-dose platinum

98 of 144

Disease-free, platinum-sensitive

Seminoma 26 of 35; non-seminoma 90 of 149

Disease-free by histology

Drugs in this study:Carboplatin (Paraplatin)Cisplatin (Platinol)Etoposide

Dose and schedule cards

High-dose carboplatin and etoposide with autologous stem-cell rescue (2 consecutive courses)

Metastatic germ cell tumour progressing after cisplatin-based chemotherapy (second line or later, including platinum-refractory disease); experienced transplant centres onlyOn the page “Testicular cancer” · Salvage treatment: relapsed or refractory disease

Metastatic germ cell tumour progressing after cisplatin-based chemotherapy (second line or later, including platinum-refractory disease); experienced transplant centres only

Drug	Dose	Route	Schedule
Carboplatin	700 mg/m²	IV	Daily for 3 consecutive days
Etoposide	750 mg/m²	IV	Daily for 3 consecutive days
Autologous peripheral-blood stem cells	—	IV infusion	After each course

Cycle length: Interval between courses: see the full text of the paper
Duration: 2 consecutive courses

Doses as in the Indiana University experience; in 110 patients, 1 or 2 cycles of VeIP (vinblastine, ifosfamide and cisplatin) were given for cytoreduction before high-dose therapy. A single high-dose course after 3 conventional cycles gave no benefit in a randomised trial. A randomised comparison with TIP as first salvage (TIGER) is ongoing. Transplant indications and conditioning.

On the page “Testicular cancer” · Salvage treatment: relapsed or refractory disease

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1High-dose carboplatin and etoposide with autologous stem-cell rescue

Two consecutive courses of high-dose chemotherapy: carboplatin 700 mg/m² and etoposide 750 mg/m², each for 3 consecutive days, each followed by an infusion of autologous peripheral-blood haematopoietic stem cells (173 patients); 11 patients received one course. In 110 patients, 1 or 2 courses of vinblastine + ifosfamide + cisplatin (VeIP) were given before high-dose therapy for cytoreduction; VeIP doses are not given in the abstract.

Source of the regimen details: Abstract of the paper (PubMed 17652649)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Consecutive patients with metastatic testicular cancer that had progressed after cisplatin-containing combination chemotherapy; including 135 patients treated in the second line, 49 in the third line or later and 40 refractory to standard-dose platinum.

Endpoints

Complete remission without relapse during follow-up; results were reported by subgroup (line of treatment, platinum sensitivity, histology), together with fatal toxicity and secondary leukaemia.

Safety and side effects

There were 3 drug-related deaths during treatment, and 3 further patients developed acute leukaemia after treatment.

Clinical significance and place in guidelines

This is the largest single-centre experience with two consecutive courses of high-dose carboplatin and etoposide and became the basis of today’s high-dose regimens in salvage treatment. In the randomised IT-94 trial, one high-dose course after 3 conventional cycles gave no benefit; the TIGER trial (TIP vs TI-CE) is examining the role of high-dose therapy as first salvage, and its results have not yet been reported.

Limitations

The study is retrospective, single-centre and without a comparison group, and patients were selected (for example, fit enough for transplant); this card is based on the abstract. VeIP doses and the interval between courses are not given in the abstract.

Original article (DOI)PubMed

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.