2004 Oncology Research and Treatment  
vs no response, visceral site: yes vs no, number of previous chemotherapy lines in metastatic disease: 1 vs 2. Efficacy was evaluated by radiological assessment every 6 wks; responses are confirmed at least 4 wks later. Results: Between 7/00 and 7/02 137 Pts have been randomized in 33 centers (68 in OXA arm and 69 in VIN arm). Main pts characteristics, safety (G 3-4 AE by pts) and efficacy (RR, PFS, OS) results are shown in the table below. The study was prematurely discontinued due to accrual
more » ... ifficulty related to competitive drugs introduced (Capecitabine ® ) in the same clinical setting. Conclusion: OXA-5FU combination achieve similar results in term of RR, PFS and OS and favorable safety profile when compared to VIN-5FU combination which is one of the most active CT regimen in post taxane MBC. 705 A phase 2 study of oxaliplatin (O) -capecitabine (C) chemotherapy in metastatic breast cancer (MBC) patients pretreated with anthracyclines and taxanes N. Background: O and C have showed an interesting activity as single agents in breast cancer patients. We carried out a phase II study to evaluate the efficacy and safety of combined O and C in anthracyclines and taxanes pretreated MBC patients. Methods: Eighteen MBC patients were treated with C 1,000 mg/sm bis in die per os, days 1 to 14 with a week of rest and O 130 mg/sm (2-hour intravenous infusion), day 1 every 3 weeks. Inclusion Criteria were: age <75, Performance Status (PS)≤2, normal kidney and liver function, absence of brain symptomatic metastases, at least two prior chemotherapy lines with anthracyclines and taxanes, informed consent. Mean age was 58 years (range, 33 to 74 years), with a median of two involved organs. Ten patients had a PS =0, 5 patients had a PS=1, 3 patients had a PS=2. The most frequent sites of disease were: liver (10 pts), skin (4 pts), bone (8 pts), pleura-lung (5 pts), lymphnodes (2 pts). Results: Fifteen patients were assessable for response and toxicity. According RECIST criteria 1 CR, 4 PR, 4 SD and 6 PD were obtained with an overall response rate of 33%. The partial responses occurred in patients with metastatic liver disease and the complete response occurred in a patient with cutaneous metastatic nodules and liver metastases. Median time to progression was 5.5 months (range 3-8 months) and median survival was 11.5 months (range 6-17 months). Hematotoxicity was prevalent but rarely severe, with only 2 patients (13.3%) with G3 neutropenia and one (6.6%) patient with G3 thrombocytopenia. G1-2 neutropenia, anemia and thrombocytopenia occurred in 5 (33%), 3(20%), and 5 (33%) patients, respectively. One third of patients developed grade 2-3 peripheral neuropathy, with grade 3 in only 2 (13.3%) patients. Nausea & vomiting G1-2 and diarrhea G1-2 were present in 6 patients. Hand-foot syndrome G2 occurred in 4 (26.6%) patients. Conclusions: From these preliminary data O/C combination seems to be effective with a favorable safety profile in anthracycline/taxane-pretreated MBC patients. Breast Cancer 660 A multistep randomized phase II/III trial comparing oxaliplatin (OXA)+5 fluorouracil (FU) to vinorelbine (VIN)+FU (FUN) after taxane (T)/anthracycline (A) failure in advanced/metastatic breast cancer (MBC) patients (pts): Final results. Background: OXA is a new DACH platinum (Pt) with preclinical evidence of activity in vivo and in mammary cell lines. Previous clinical study has shown promising activity both for OXA alone (Ann Oncol 2001 Feb 12(2):179-82) and with FU (JCO 2002 15;20:2551-8) in pretreated MBC. Methods: In order to compare tolerance and activity of OXA/FU to reference regimen FUN in pts pretreated with both T and A, we conduct a randomized phase II-III trial. Pts are assigned either to OXA 130 mg/m 2 2 hours IV on day (D) 1 plus FU 750 mg/m 2 daily by continuous IV infusion D1 to D5 q 3 wks or VIN 25 mg/m 2 IV bolus plus the same FU. Eligibility criteria included relapsing progressive MBC, at least one previous chemotherapy (CT) for MBC, no more than 3 prior CT, previous A, previous T therapy given for MBC in an appropriate dose and schedule, at least one measurable target lesion (RECIST criteria), WHO PS 0-2, adequate baseline organs functions. Stratification factors: institution, best response Onkologie 2004;27(suppl 1):12-58 Background: Expression of key enzymes in chemotherapy drug pathways correlates with CRC response following treatment. No prior research has simultaneously described the patterns of expression in CRC for 5-fluorouracil, irinotecan and oxaliplatin pathways. Characterizing relative expression levels of these enzymes is a first step towards definitively predicting tumor responsiveness to chemotherapy. Methods: Twelve genes known to influence tumor response to chemotherapy were selected from the pharmacogenetic pathways of 5-fluorouracil, irinotecan and platinum agents. Genes included intracellular targets, DNA repair enzymes, drug transporters and metabolizers. Gene expression was examined in primary colorectal adenocarcinoma and adjacent normal mucosa in 51 patients with stage III or IV disease using TaqMan RT-PCR. Relative expression levels were calculated with β-actin as control using a method to account for differing polymerase amplification efficiencies. Results: TYMS, ERCC1 & 2, GSTP1, TOP1, and UGT1A1 were significantly over-expressed in tumor cells relative to normal mucosa, while CES2, DPYD and ABCG2 were under-expressed (p <0.05, Wilcoxon matched pairs test). Expression of ABCB1, ECGF and CYP3A4 did not differ significantly between tumor and normal tissues. Expression of enzymes regulating platinum-agent metabolism and DNA repair were co-regulated. Using differential expression relative to normal mucosa as a marker for tumor resistance, predicted tumor response rates were calculated. 19.6% of tumors were predicted responsive to single-agent irinotecan, 7.8% to 5-FU, and 15.7% to oxaliplatin. Two-thirds were predicted resistant to all three drugs. Conclusions: Significant differences in gene expression were found between CRC and normal mucosa. Distinct sensitivity subgroups existed among the 51 patients with pathologically homogenous disease. These preliminary observations allow further research to correlate multivariate gene expression with clinical outcomes in order to develop a model for predicting response to chemotherapy, eventually resulting in patient-specific treatment. Purpose: This trial has been designed in order to establish potential pharmacokinetic (PK) interaction between Oxaliplatin (Oxa)and Xeloda (Xel) when administrated in combination and to monitor neurological toxicity when Oxa is administered over 6 hours infusion. Treatment schedule: Oxa 130 mg/m 2 6 hours perfusion at day 1, Xel 1000 mg/m 2 twice daily at day 2 to 15. Treatment repeated every 22 days if >1000 neutrophiles and >100 000 platelets and no other G 3-4 non hematological toxicity. PK analysis were performed at day 1 and 15; receptor for IL 6 at day 1. Blood sampling was done -on day 1 (30min before the end of infusion and 1h30min after the end of infusion in order to validate the Pk population model we recently published for Oxa). On day 2, 30min, 1h, 2h and 4h after Xel. Xel, dFdC, dFdU, 5FU and FBAL were monitored by HPLC and GC-MS in order to determine potential metabolic interaction with Oxa. On day 14, 30min, 1h, 2h and 4h after Xel in order to compare adsorption and PK of Xel and metabolites with and without Oxa. Results: Between April 2003, and December 2003, 10 patients with advanced colo-rectal cancer were included, in first line chemotherapy for metastatic disease, 3 males and 7 females, 7 colon cancer and 3 rectum, medium age 56 (46 to 66): PS 0=7, PS 1=2, PS 2=1; liver involvement in 8 patients (80%) and lung in 4 patients (40%); median cycles 4 (1 to 9). Toxicity = 3 pts Grade III diarrhea, 1 heart pain at day 2 of first cycle and 1 Onkologie 2004;27(suppl 1):12-58 Abstracts unexplained death. No hand-food syndrome was observed in this population. Only mild paresthesia in 2 Pts (20%)after 7 cycles Efficacy: 2 CR, 2 PR and 2 stabilizations. PK and IL6 receptor results will be presented. So far, 2 plasma samples are enough to extrapolate AUC of ultrafilterable Oxa according our model. Pk of Xel and metabolites are currently evaluated and Pk interaction between Oxa and Xel will be analysed. Conclusion: This combination is active, easy to administer and very well tolerated especially without significant neurological toxicity when Oxa is infused over 6 hours. Moreover, 2 blood samples are sufficient to monitor Oxa Pk according to the population Oxa parameters and to consider posology adaptation in further trials
doi:10.1159/000080548 fatcat:5d6ffjxec5hgdpwvuviw4jctmu