High-dose
chemotherapy (HD-CT) has a role in the potentially curative treatment of several tumours. The relative efficacies of the different regimens have not been studied in comparative trials, but it is clear that toxicities differ significantly between them. We analysed the immediate and long-term toxicity in the first 100 consecutive patients treated with the
CTC regimen (
cyclophosphamide 6000 mg m(-2),
carboplatin 1600 mg m(-2) (or 20 mg ml(-1) min under the curve (AUC)) both as daily 1 h infusion,
thiotepa 480 mg m(-2) as twice daily 30 min infusion, all divided over 4 consecutive days) followed by peripheral blood progenitor cell reinfusion (PBPC-Tx). Most patients had high-risk (n=86) or metastatic (n=4)
breast cancer, or a germ cell tumour (n=8). Two patients (with a
medulloblastoma and an
aesthesioneuroblastoma, respectively) received CTC as off-protocol salvage regimen. The main toxicity was bone marrow suppression. Most patients had PBPC-Tx with
granulocyte colony-stimulating factor (
G-CSF), and the median time to neutrophil count 500 x 10(6) l(-1) and platelet count >20 x 10(9) l(-1) without transfusion independence was 10 (range 8-25) and 13 (8-60) days, respectively. The toxic death rate was 1%. Other frequent toxicities were neutropenic
fever requiring
antibiotics (n=65), central
catheter-related infection (n=12) or a
bleeding episode (n=48), mostly
epistaxis (n=26). Reversible
cardiac toxicity was seen in six patients and pulmonary events occurred in seven patients (
infection (n=6),
embolism (n=1)). Grade 3-4 gastrointestinal toxicity was frequent:
nausea and
vomiting 55%, diarrhoea 28% and mild liver toxicity (
transaminase elevations) 9%. One patient pretreated with
cisplatin had a
kidney transplantation 8 years after HD-CT. Late complications included reversible
radiation pneumonitis (n=12) and chronic
heart failure (n=2). We found five second solid
malignancies and two myelodysplasias. In conclusion, the
CTC regimen is associated with a moderate, mainly reversible, toxicity. Future studies need to compare the efficacy and toxicity of the different HD-CT regimens.