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Neurotoxicity represents a major complication of oxaliplatin. This study aimed to identify early clinical markers of oxaliplatin neurotoxicity, in comparison with cisplatin, and detect predictors of chronic neuropathy. Forty-eight patients with mainly colorectal cancer were evaluated prospectively before oxaliplatin (n=28) or cisplatin (n=20) administration and then 2 weeks after the third (C3), sixth (C6) and ninth (C9) cycles. Eighteen oxaliplatin patients were re-assessed at 12+/-2 months. Evaluation included quantitative sensory testing, i.e., detection/pain thresholds for mechanical, vibration, cold and heat stimuli; pain induced by suprathreshold cold (5-25 degrees C) and heat (38-48 degrees C) stimuli and quantified assessment of symptoms (neuropathic pain symptom inventory). Symptoms of oxaliplatin neurotoxicity (cold-triggered dysesthesia of the hands; 96% of the cases) were reversible between cycles for up to C6. In contrast, thermal testing identified sustained (irreversible between cycles) neurotoxicity two weeks after C3 in the oxaliplatin group only, characterized by hyperalgesia to cold (5-25 degrees C) (F=11.4; p=0.0002 relative to cisplatin patient responses in the hand) and heat stimuli (38-48 degrees C) (F=4.1; p=0.049 for the hand). Cold-evoked symptoms lasting 4 days or more after C3 predicted chronic neuropathy (OR: 22; 95% CI: 1.54-314.74; p=0.02) whereas enhanced pain in response to cold (20 degrees C stimulus on the hand) predicted severe neuropathy (OR: 39; 95% CI: 1.8-817.8 p=0.02). Thermal hyperalgesia is a relevant clinical marker of early oxaliplatin neurotoxicity and may predict severe neuropathy.

Background Combination chemotherapy with continuous 5-fluorouracil (5-FU) and cisplatin in a monthly regimen is one of the standard treatments for advanced gastric carcinoma. This study evaluated the new LV5FU2-P regimen, designed to improve efficacy and tolerance of the 5-FU plus cisplatin combination. Patients and methods Forty-three patients with advanced or metastatic gastroesophageal junction or gastric carcinoma were prospectively included in the study. They were treated every 14 days with cisplatin 50 mg/m2 on day 2 plus folinic acid 200 mg/m2/day as a 2-h intravenous (i.v.) infusion on days 1 and 2, plus bolus 5-FU 400 mg/m2/day on days 1 and 2, plus continuous 5-FU 600 mg/m2/day as a 22-h i.v. infusion on days 1 and 2. Ten patients received a simplified regimen (folinic acid 40 mg/m2 day 1 + bolus 5-FU 400 mg/m2 day 1 + continuous 5-FU 2400 mg/m2 on days 1 and 2 with cisplatin 50 mg/m2 on day 2). Results All the patients were assessable for response and 42 for toxicity. One patient achieved a complete response and 15 a partial response, for an overall response rate of 37.2% [95% confidence interval (CI) 22.1% to 52.3%]. The median progression-free survival was 7.2 months (95% CI 5.4–10.9) and the overall survival was 13.3 months (95% CI 10.1–16.4). There were no treatment-related deaths. Hematological and gastrointestinal toxicities were the most common severe toxicities. Conclusions LV5FU2-P is an active and well tolerated regimen in the treatment of advanced gastroesophageal junction or gastric carcinomas. It warrants evaluation comparatively with other active regimens.

Background Unresectable biliary tract carcinoma (BTC) is associated with a very poor prognosis. To improve efficacy and tolerance of the 5-fluorouracil (5-FU)/cisplatin combination in BTC, we designed a new therapeutic schedule, the LV5FU2-P regimen. Patients and methods Twenty-nine patients with advanced or metastatic BTC were prospectively enrolled in the study. The treatment (LV5FU2-P regimen) consisted of a biweekly administration of a 2‐h infusion of leucovorin 200 mg/m2, a 400 mg/m2 bolus of 5-FU followed by a 22-h continuous infusion of 600 mg/m2 5-FU on two consecutive days and cisplatin 50 mg/m2 on day 2. Clinical symptoms, performance and weight changes were monitored. Results Objective responses were observed in 10 patients (34%) (95% confidence interval 23% to 45%) including one complete response and nine partial responses (stabilization 38%, progression 28%). Median progression-free survival and overall survival were 6.5 and 9.5 months, respectively. Weight gain was observed in 45% of patients and performance status improved in 60%. One patient had a grade 4 thrombocytopenia, and grade 3 toxicity occurred in 41% of patients. There were no treatment-related deaths. Conclusions This study, one of the largest phase II trials performed for this disease, shows that the LV5FU2-P regimen is an active and well-tolerated chemotherapy for advanced and metastatic BTC.

13533 Background: The BOND study demonstrated Cetuximab (Cx) activity in irinotecan-refractory metastatic colorectal cancer (IRMCCR) patients (pts). Cx was approved in Europe early 2004 for this population. The aim of this study was to survey its efficacy in a unselected population of IRMCCR treated in 4 french academic centers. Methods: Data of all IRMCCR pts who had received Cx with or without irinotecan regimen between Jan 2004 and Sept 2005 were included in this survey. Exhaustivity of treated pts was established based on pharmacy registry. Primary end-point was time to tumor progression (TTP). Secondary end-points were overall survival (OS) and tumor response (RECIST). Results: Characteristics of the 76 included IRMCCR pts were : male/female : 44/32; median age 59.5 yrs (range 23 - 79); performance status : 0–1 (59 pts) and 2–3 (17); median number of tumor sites : 2 (1 - 5). The median number of chemotherapy regimens preceeding first Cx administration was 3 (range 1 to 5). At least one local treatment of the metastases (surgical resection and/or radiofrequency ablation) was a part of the strategy before Cx for 39 pts (51.3%). EGFR status was positive in 72 pts and negative in 4. Cx was administered : alone in 4 pts, combined with FOLFIRI in 4 and with irinotecan alone in 68 (89%). 10 pts received only one infusion Cx (early clinical progression : 6; patient decision : 2; early death : 2). Median number of Cx infusions was 10 (range 1 to 60). Median TTP (intent-to-treat) was 3.3 months [IC95% : 2.2–4.6]. Median OS since first-line chemotherapy and first Cx administration were 33.6 months [IC95% : 27.7–41.1] and 7.6 months [IC95% : 5.6–9.5], respectively. Tumor response (full population) was complete response 1.3%, partial response 19.7% (overall response 21%), stable disease 25% (disease control : 46%), progression 37% and not evaluable 17%. Conclusions: This therapeutic survey in a unselected population of IRMCCR are in accordance with the results of the BOND study for TTP, OS and tumor response. (supported by ADEBIOPHARM ER48). [Table: see text]

Fat embolism of necrotic bone marrow could be a frequent cause of acute chest syndrome (ACS) in sickle cell syndromes (SC), as suggested by postmortem findings. To check this hypothesis in living patients, we evaluated the presence of fatty macrophages recovered by bronchoalveolar lavage (BAL) in ACS. We investigated 20 consecutive cases of ACS by BAL, and identification of alveolar cells containing fat droplets was performed using oil red O (ORO), a specific neutral fat stain. The specificity of the method was determined on control groups, including eight SC patients without acute chest syndrome and 15 non-SC patients. A cut-off of5% of alveolar macrophages containing fat droplets was determined from the control groups to assess the diagnosis of fat embolism. In 12 ACS episodes, BAL exhibited5% of fatty macrophages, ranging from 10% to 100% (median value 46.5%). In 11 cases, fat embolism was associated with proven (n = 8) or probable (n = 3) bone marrow infraction, which mostly predated ACS. Eight ACS episodes were associated with a low percentage (or = 5%) of fatty alveolar macrophages and could be related to a cause other than fat embolism in six episodes, such as sepsis, in-situ thrombosis, or rib infarcts generating hypoventilation. This study supports the diagnostic yield of BAL for fat embolism, which can be incriminated in 60% of cases of ACS in this adult population.