Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer: a feasibility study

Abstract

Summary The tolerability and efficacy of four courses of paclitaxel and ifosfamide plus cisplatin every 3 weeks was evaluated in patients with residual or refractory ovarian cancer. Additionally, supportive haematological effects of recombinant human interleukin 3 (rhlL-3) and recombinant human granulocyte colony-stimulating factor (G-CSF) were studied. Paclitaxel starting dose was 135 mg m-2 (day 1), with ifosfamide dose 1.2 g m-2 day-1 (days 2-4) and cisplatin dose 30 mg m-2 day-1 (days 2-4). All 16 patients received 5.0 9g kg-1 day-' G-CSF (days 7-16) and, in addition, eight patients were randomized to receive 10 gg kg-' day-' rhlL-3 (days 5-9). Paclitaxel and ifosfamide doses were reduced when grade IV haematological toxicity occurred. In the absence of grade IV haematological toxicity and normal recovery of haematopoiesis, paclitaxel dose was escalated. Toxicity was evaluable in 56 courses, with haematological effects in 52. Despite antiemetic treatment, nausea and vomiting (2 grade 1) occurred in 50 courses. Five patients had persisting peripheral neuropathy. Renal and liver function were not affected. Grade IV neutropenia occurred in 12 out of 52 courses, with neutropenic fever in two patients, both of whom died from fatal septicaemia. Grade IV thrombocytopenia without bleeding was observed in 15 courses. Grade IV haematological toxicity was associated with hepatic metastases and concurrent increases in alkaline phosphatase (P <0.001) and gamma-glutamyltransferase (P=0.007). No relation was found between haematological toxicity and pharmacokinetic parameters of paclitaxel. Patients treated with rhlL-3 showed a tendency to a faster platelet recovery (not affecting platelet nadir), and the cisplatin dose intensity was higher (P=0.025). Six of the nine evaluable patients had a tumour response. The overall median progression-free survival was 7 months and the overall mean survival was 13 months. In conclusion, this potentially interesting combination as second-line treatment showed a low tolerability with unexpected mortality, while rhlL-3 administration tended to induce a more rapid platelet recovery.

High dose single-agent paclitaxel in a hemodialysis patient with advanced ovarian cancer: a case report with pharmacokinetic analysis and review of the literature

“…In our patient, when paclitaxel was given at 175 mg/m 2 , the mean values for C max , AUC 0→∞ , and CL T with 3363.0 ng/mL, 12,200 ng·h/mL, and 14 L/h/m 2 , respectively, were comparable with the mean values previously reported for the same dosage and schedule of the drug in patients with nonperturbed excretory function (2,18,19) (Tables 2 and 4).…”

Salvage chemotherapy with a combination of paclitaxel, ifosfamide, and cisplatin for the patients with recurrent carcinoma of the uterine cervix

“…In our current study, 21 patients (39.6%) with previous chemotherapy for recurrent disease were included and they showed much a higher incidence of neurotoxicity (68% vs 55%, respectively). According to Veldhuis et al (31) , both paclitaxel‐ and cisplatin‐induced neurotoxicities are cumulative and dose related. Another possible explanation may be the different dose schedule of the regimen.…”

Ifosfamide, paclitaxel and cisplatin first-line chemotherapy in advanced, suboptimally debulked epithelial ovarian cancer

“…In one study, ifosfamide was combined with vinblastine and gallium nitrate, 34 whereas in two other studies ifosfamide was combined with cisplatin and paclitaxel. 35,36 Based on these data, we decided to evaluate the activity of a three-drug regimen consisting of ifosfamide, paclitaxel, and cisplatin in previously untreated patients who had suboptimally debulked Stage III or IV EOC. In our current Phase II study, we administered paclitaxel at a dose of 175 mg/m 2 intravenously over a 3-hour period on Day 1, ifosfamide 1500 mg/m 2 intravenously over 1 hour on Days 1-3 (with MESNA uroprotection), and cisplatin 75 mg/m 2 intravenously over 2 hours on Day 2.…”

“…In this study, paclitaxel and cisplatin were given at the same doses as in our Phase II trial, whereas ifosfamide was infused at a dose of 5 g/m 2 over 24 hours. Myelotoxicity was the most relevant side effect in the study of Veldhuis et al 35 who used the same drug combination as a second-line treatment for patients with residual or relapsing ovarian carcinoma. Zanetta et al 52 observed Grade 3 or 4 neutropenia in 91% of patients with recurrent or persistent squamous cell cervical cancer treated by paclitaxel, ifosfamide, and cisplatin.…”

“…One patient had Grade 3 CNS toxicity (lethargy). Colombo et al 44 observed Grade 3 or 4 neurotoxicity in 24% of patients, whereas Veldhuis et al 35 observed sensor neurotoxicity in 44% of patients who received the paclitaxel, ifosfamide, and cisplatin combination regimen. To avoid excessive neurotoxicity, cisplatin could be substituted by carboplatin, and paclitaxel could be infused over 24 hours.…”