Two meta-analyses have suggested that the addition of an
anthracycline to
platinum-based
chemotherapy may improve survival in advanced
ovarian cancer, and two randomised trials have demonstrated superiority of
paclitaxel over
cyclophosphamide in
platinum combinations. A combination of
platinum,
anthracycline and
paclitaxel would, therefore, be a reasonable experimental arm of any future randomised trial in patients with
epithelial ovarian carcinoma (EOC). Patients who required
chemotherapy for EOC but were ineligible for standard trials or had other gynaecological tumours that required similar
platinum-based
chemotherapy were considered for this pilot. The
platinum/
anthracycline/
paclitaxel regimen (G-CAT) was given 3-weekly and consisted of
doxorubicin 50 mg/m(2) or
epirubicin 60 mg/m(2) intravenously (i.v.) bolus,
paclitaxel 175 mg/m(2) (i.v.) over 3 h and either
cisplatin 75 mg/m(2) (i.v.) or
carboplatin AUC 6, with
granulocyte colony-stimulating factor (
G-CSF) at the neutrophil nadir. Different combinations were used in order to determine the least toxic regimen. Toxicity and response were assessed according to CTC and WHO criteria, respectively. 26 patients entered the study, 13 with EOC and 13 with other gynaecological
cancers (peritoneal, fallopian tube, mixed Mullerian). Median age was 49 years (range: 27-67). 8 patients received
carboplatin/
doxorubicin/
paclitaxel, 8
cisplatin/
doxorubicin/
paclitaxel and 10
carboplatin/
epirubicin/
paclitaxel. A total of 135 cycles of
chemotherapy were delivered, with a median of 6 cycles per patient (range: 2-6). 54 (40%) cycles required
G-CSF support and 17 (65%) patients required at least one
dose reduction. All patients experienced grade 4
neutropenia and 13 (50%) patients developed grade 3-4
thrombocytopenia (12 of whom had received
carboplatin). There were 4 (15%) patients with grade 3/4
infections but no septic deaths. Non-haematological toxicities were manageable,
lethargy occurred in 75% of
cisplatin-treated patients. Grade 1/2
cardiotoxicity, as assessed pre- and post-treatment by left ventricular ejection fraction, was observed in 6/13 (46%) patients who had received
doxorubicin and 2/7 (29%)
epirubicin-treated patients. No clinically detectable
cardiac toxicity was encountered. The response rate in 25 evaluable patients was 76% (12 CR, 7 PR). Dose intensity was highest in the
carboplatin/
epirubicin/
paclitaxel combination. G-CAT shows high activity and can be administered safely, but only very fit patients are suitable for this regimen as it is associated with considerable toxicity.
Carboplatin/
epirubicin/
paclitaxel was the best tolerated regimen overall.