Hepatic Resection After Rescue Cetuximab Treatment for Colorectal Liver Metastases Previously Refractory to Conventional Systemic Therapy

Purpose In patients with unresectable colorectal liver metastases (CLM) resistant to first-line chemotherapy, the impact of cetuximab therapy on resectability is unknown. This study was performed to determine the post-cetuximab resectability rate and to examine postoperative outcomes for these heavily pretreated patients. Patients and Methods From February 2004 to April 2006, we evaluated 151 patients with unresectable CLM resistant to initial chemotherapy and subsequently treated with systemic cetuximab. Resectability rates, patient outcomes, and tumoral and nontumoral liver pathology were assessed. Results A total of 27 patients underwent surgery after a median of six cycles of cetuximab + irinotecan (20 of 27), oxaliplatin (four of 27), or both (one of 27). Eighteen patients (67%) had experienced treatment failure after at least two lines of chemotherapy before cetuximab. Twenty-five of the 27 patients who had surgery underwent hepatectomy: nine of 133 patients who were treated completely at our institution (resectability rate, 7%) and 16 of 18 patients who were referred from other institutions after systemic cetuximab therapy. Postoperative mortality was 3.7% (one of 27), with a complication rate of 50%. Histopathologic liver abnormalities were found in nine patients (36%), without specific lesions attributable to cetuximab. After median follow-up of 16 months, 23 of 25 patients who underwent resection (92%) were alive, and 10 patients (40%) were disease free. Median overall (OS) and progression-free survival (PFS) from initiation of cetuximab therapy were 20 and 13 months, respectively. Conclusion For CLM refractory to conventional chemotherapy, combination therapy with cetuximab increases resectability rates without increasing operative mortality or liver injury. The median OS and PFS of 20 and 13 months, respectively, suggest that this novel oncosurgical strategy benefits patients with previously refractory disease who respond subsequently to cetuximab.

Hepatic resection following rescue cetuximab treatment for colorectal liver metastases previously refractory to conventional systemic therapy

4061 Background: The impact of cetuximab-containing chemotherapy on resectability of previously unresectable colorectal liver metastases (CLM) is unknown, especially in patients resistant to first-line chemotherapy. This study was performed to determine the cetuximab resectability rate, and to examine the outcomes of these heavily pretreated patients after hepatic resection. Methods: From February 2004 to April 2006, we evaluated 151 patients with unresectable CLM resistant to initial chemotherapy and subsequently treated with cetuximab-containing regimens. 133 patients (88%) were completely treated at our institution and 18 patients (12%) received systemic therapy elsewhere. Resectability rates, perioperative outcomes, survivals, and histopathological analysis of the tumoral and non- tumoral liver were assessed. Results: 27 patients were operated after a median of 6 cycles of cetuximab + irinotecan (20/27), oxaliplatin (4/27), or both (1/27). 18 of these patients (67%) had failed at least 2 lines of prior chemotherapy. 25 patients underwent hepatectomy, including 9 of 133 patients completely treated at our institution (resectability rate: 7%) and 16 of 18 referred patients. Postoperative mortality was 3.7% (1/27), with a complication rate of 50%. Complete tumor necrosis was observed in 2 patients (8%). Histopathological liver abnormalities were found in 9 patients (36%), without any specific lesion related to cetuximab. After a median follow-up of 16 months (range 6–39), all but one resected patients were alive, 10 of whom were disease-free. Conclusions: For CLM refractory to conventional chemotherapy, combination chemotherapy with cetuximab significantly increased resectability rates with no appreciable increase in operative mortality or liver injury. Longer follow-up is awaited to confirm the encouraging results of this new oncosurgical strategy. No significant financial relationships to disclose.

Neoadjuvant chemotherapy for resectable adenocarcinoma of the panctreatic head - a prospective phase II trial

4610 Background: Pancreatoduodenectomy alone was considered the standard treatment for resectable adenocarcinoma of the pancreatic head in Europe. Recently adjuvant chemotherapy without radiation has become a new standard worldwide. Neoadjuvant chemotherapy has advantages over adjuvant chemotherapy. Methods: Patients (pts) with histologically or cytologically confirmed ductal adenocarcinoma of the pancreatic head judged to be resectable were entered into this single center prospective phase II trial. After written informed consent staging with thoracic/abdominal CT-scans, endoscopic ultrasound, PET-CT and diagnostic laparoscopy were performed. Preoperative chemotherapy consisted of 4 treatments with gemcitabine (1,000mg/m2) and cisplatin (50mg/m2) every 2 weeks. Re-staging was followed by (classic or pylorus-sparing) pancreatoduodenectomy about 8 weeks after the start of chemotherapy. CA 19- 9, prealbumin serum levels, and quality of life (QLQ-30) were also assessed before and after chemotherapy. The primary study end-point was the resectability rate. Results: Twenty-eight pts entered this trial between June 2002 and January 2007, 27 have completed chemotherapy. The resectability rate after chemotherapy was 93% (25/27). Neoadjuvant chemotherapy was well tolerated, although 7 episodes of transient Grade III/IV toxicities occurred in 5 pts. While median recurrence-free survival from diagnosis was 9.2 months (95% CI 7.7–10.8), median overall survival was an excellent 26.5 months (12.2–40.8). CA 19–9 serum levels decreased by 48% (p=0.01) after neoadjuvant chemotherapy, while overall quality of life increased by 24% (p=0.02). Nutritinoal status also improved: Prealbumin levels were normal in 89% after chemotherapy compared to 60% before (p=0.02). Conclusions: Neoadjuvant gemcitabine/cisplatin for two months is well tolerated and does not jeopardize surgical resectability in adenocarcinoma of the pancreatic head. Furthermore, it offers several advantages over primary surgery including patient selection, improvements in nutritional status and quality of life. We are currently planning a randomized study comparing the combination of neoadjuvant and adjuvant chemotherapy versus adjuvant treatment alone. No significant financial relationships to disclose.

The clinicopathological and socioeconomic features of patients with gastric cancer in Turkey (Turkish Oncology Group)

20098 Background: The incidence of gastric cancer has declined dramatically in western countries. However it is the second most common cancer in Turkey, and its mortality rate is still high. The aim of this study was to evaluate the clinicopathological and socioeconomic features of patients with gastric cancer in Turkey. Methods: A questionnaire including the clinicopathological and socioeconomic features of gastric cancer patients diagnosed in 2004, was used in this retrospective multicentre study. The characteristic of patients in economically developed Western Turkey (WT) was compared to those in less developed Eastern Turkey (ET). Results: From sixteen centers, 971 patients with gastric cancer during the year 2004 were included in the study. Male-female ratio was 2/1. Mean age was 57 ± 12.9 years. Of patients, 75.3% had low socioeconomic status. Distal and middle gastric cancers were the most common locations (distal 39%, middle 36.5% vs upper 24.5%). The R0 resectability rate was 54.1% in all patients. There was no statistically significant difference in gender, age, smoking rate, anemia, the location of tumor and the frequency of atrophic gastritis between WT and ET. The rate of cancer resectability was lower in Eastern Turkey (ET) than Western Turkey (WT) (31.6% vs. 63.4%, p = 0.0001). Also, socioeconomic status of patients was lower in ET than those in WT (53.6% vs. 32.3%, p = 0.0001). H. pylori associated gastritis and intestinal metaplasia were more common in ET when compared with WT (75.0% vs. 40.5%, P = 0.003, and 68.4% vs. 18.1%, respectively, P = 0.0001). Conclusions: Lower socioeconomic status and lower resectability rate of gastric cancer in ET is considerable. Further epidemiological study of gastric cancer is warranted in Turkey. No significant financial relationships to disclose.