FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG)

To compare the efficacy and toxicity of oxaliplatin (L-OHP) in combination with irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin (LV) (FOLFOXIRI) vs irinotecan and 5-FU/LV (FOLFIRI) as first-line treatment of patients with metastatic colorectal cancer (MCC). A total of 283 chemotherapy-naïve patients with MCC were enrolled (FOLFIRI arm: n=146; FOLFOXIRI arm: n=137). In the FOLFOXIRI arm, CPT-11 (150 mg m−2) was given on d1, L-OHP (65 mg m−2) on d2, LV (200 mg m−2) on days 2 and 3 and 5-FU (400 mg m−2 as i.v. bolus and 600 mg m−2 as 22 h i.v. continuous infusion) on days 2 and 3. In the FOLFIRI arm, CPT-11 (180 mg m−2) was given on d1 whereas LV and 5-FU were administered in the same way as in the FOLFOXIRI regimen. Both regimens were administered every 2 weeks. There was no difference in terms of overall survival (median OS: 19.5 and 21.5 months, for FOLFIRI and FOLFOXIRI, respectively; P=0.337), median time to disease progression (FOLFIRI: 6.9 and FOLFOXIRI: 8.4 months; P=0.17), response rates (33.6 and 43% for FOLFIRI and FOLFOXIRI, respectively; P=0.168). Patients treated with FOLFOXIRI had a significantly higher incidence of alopecia (P=0.0001), diarrhoea (P=0.0001) and neurosensory toxicity (P=0.001) compared with patients treated with FOLFIRI. The present study failed to demonstrate any superiority of the FOLFOXIRI combination compared with the FOLFIRI regimen, although the observed median OS is one of the best ever reported in the literature

A dose escalation and pharmacokinetic study of biweekly pegylated liposomal doxorubicin, paclitaxel and gemcitabine in patients with advanced solid tumours

To determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of pegylated liposomal doxorubicin (PLD), paclitaxel (PCX) and gemcitabine (GEM) combination administered biweekly in patients with advanced solid tumours. Twenty-two patients with advanced-stage solid tumours were treated with escalated doses of PLD on day 1 and PCX plus GEM on day 2 (starting doses: 10, 100 and 800 mg m−2, respectively) every 2 weeks. DLTs and pharmacokinetic (PK) parameters of all drugs were determined during the first cycle of treatment. All but six (73%) patients had previously received at least one chemotherapy regimen. The DLT dose level was reached at PLD 12 mg m−2, PCX 110 mg m−2 and GEM 1000 mg m−2 with neutropaenia being the dose-limiting event. Of the 86 chemotherapy cycles delivered, grade 3 and 4 neutropaenia occurred in 20% with no cases of febrile neutropaenia. Non-haematological toxicities were mild. The recommended MTDs are PLD 12 mg m−2, PCX 100 mg m−2 and GEM 1000 mg m−2 administered every 2 weeks. The PK data revealed no obvious drug interactions. Biweekly administration of PLD, PCX and GEM is a well-tolerated chemotherapy regimen, which merits further evaluation in various types of solid tumours

Small Cell Ovarian Cancer in Adolescents: Report of Two Cases and Review of the Literature

Ovarian small cell carcinoma is a rare and highly malignant neoplasm carrying a poor prognosis. Although combination chemotherapy remains the cornerstone of treatment due to the rarity of these tumors, no regimen can be recommended as standard of care although in the majority of cases platinum-based regimens are used. Herein, we report two cases of small cell carcinoma of the ovaries along with a review of the relevant literature

A dose-escalation study of pegylated liposomal doxorubicin and oxaliplatin in patients with advanced solid tumors

Purpose: A phase I study was conducted to determine the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of the pegylated liposomal doxorubicin (PLD) and oxaliplatin combination in patients with advanced solid tumors. Patients and Methods: Forty-five patients with advanced-stage solid tumors received escalating doses of PLD 25-50 mg/m2 as 60-min intravenous (i.v.) infusion and oxaliplatin 80-130 mg/m2 as 2- to 4-hour i.v. infusion on day 1 every 3 weeks without growth factors. Results: MTD was defined at PLD 45 mg/m2 and oxaliplatin 130 mg/m2. Eleven dose levels were evaluated and DLTs were grade 2-3 neutropenia resulting in treatment delays, grade 3 neurotoxicity and nausea/vomiting. A total of 187 cycles were administered with two episodes of febrile neutropenia and one toxic death due to sepsis. Two (4%) and 6 (13%) patients developed grade 4 and 3 neutropenia, respectively, 2 (4%) and 1 (2%) grade 4 and 3 thrombocytopenia, and 1 (2%) grade 4 anemia. The most common nonhematological toxicities were grade 2-3 nausea/vomiting and asthenia observed in 27 (60%) and 16 (36%) of patients, respectively. One complete and eight partial responses were observed. Conclusion: The combination of PLD and oxaliplatin has an acceptable toxicity profile with promising activity and merits further evaluation in phase II studies. Copyright © 2006 S. Karger AG