Phase II study of figitumumab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: clinical activity and molecular response (GORTEC 2008-02).

BACKGROUND: Preclinical studies suggest that insulin-like growth factor-1 receptor (IGF-1R) blockage could be a promising therapeutic target in squamous cell carcinoma of the head and neck (SCCHN). Therefore, we investigated the efficacy and toxicity of figitumumab, an anti-IGF-1R monoclonal antibody, in palliative SCCHN. PATIENTS AND METHODS: Patients with palliative SCCHN progressing after platinum-based therapy were treated with figitumumab i.v. 20 mg/kg, every 3 weeks. The primary end point was the disease control rate at 6-8 weeks after treatment initiation. Tumor biopsies and plasma samples were collected before and after figitumumab administration to monitor the molecular response. RESULTS: Seventeen patients were included. Only two patients achieved stable disease at 6-8 weeks. Median overall survival and progression-free survival were 63 and 52 days, respectively. The main grade 3-4 adverse event was hyperglycemia (41%). Translational research showed that figitumumab downregulated IGF-1R at the surface of tumor cells with activation of the epidermal growth factor receptor (EGFR) pathway, as shown by the upregulation of p-EGFR in tumor cells (P=0.016), and an increase in the plasma level of tumor growth factor-alpha (P=0.006). CONCLUSION: Figitumumab monotherapy has no clinically significant activity in unselected palliative SCCHN.

Prognostic implications of downstaging following preoperative radiation therapy for operable T3-T4 rectal cancer.

PURPOSE: To evaluate the prognostic value of tumor downstaging after preoperative radiation for resectable rectal cancer. METHODS AND MATERIALS: Eighty-eight patients with non-metastatic resectable rectal cancers (76 T3 and 12 T4) were treated with preoperative irradiation. Median dose was 40 Gy (30-46 Gy) delivered over 32 days (range 11-40). Seventeen patients received preoperative chemotherapy, two courses of 5-fluorouracil (5FU) 350 mg/m2/day and folinic acid 20 mg/m2/day; 5 days per week during the first and fifth weeks of radiotherapy. Surgery was performed with a mean delay of 46 days after completion of irradiation and included 66 abdominoperineal resections and 22 anal sphincter-preserving procedures. Postoperative chemotherapy was administered in 44 patients. RESULTS: Histological tumor stages were: complete histological response in 7%, pT2N0 in 19%, pT3N0 in 46%, and pT2-3N1 in 28%. Tumor downstaging occurred in 26%. No predictive factor of downstaging was statistically significant. The median follow-up was 33 months. The 3- and 5-year cancer-specific survival rates were 100% for the pT0N0 and pT2N0, respectively, 89% and 68% for pT3N0, and 64% and 0% for pT2T3N1. After preoperative irradiation, the pathological tumor stages remained a prognostic factor. Patients with downstaging (pT0T2N0) had significantly higher cancer-specific survival rates than the group without downstaging: 100% and 80% at 3 years, and 100% and 45% at 5 years; respectively (p = 0.011). The 3- and 5-year recurrence free-survival rates were 94% for the group with downstaging and 56% and 50%, respectively, for the group without downstaging (p = 0.002). CONCLUSION: Downstaging after preoperative irradiation in this retrospective study results in an improvement in local control and survival.

Brain metastases from epithelial ovarian carcinoma.

BACKGROUND: Brain metastases from epithelial ovarian carcinoma are rare. We reviewed our experience to evaluate the results of different treatments and their prognosis. Discussion is based on a review of the literature. METHODS: From 1974 to 1998, eight of 704 patients treated for epithelial ovarian carcinoma at our large cancer center developed brain metastases. The median time before occurrence of brain metastases was 15 months after the diagnosis of the ovarian cancer. Six patients had a single lesion and two had multiple parenchymal lesions. Brain was the only site of disease in one patient, while seven had concomitant dissemination. Seven out of eight patients underwent a treatment for brain metastases. The treatment consisted of either radiotherapy (2 cases), chemotherapy (2 cases), surgery and radiotherapy (1 case), or combined treatment of the three modalities (2 cases). RESULTS: Median survival from diagnosis of brain lesions was 3 months (range 1-12). One patient without treatment died one month later. Survival after complete surgical resection and radiotherapy was 12 months. One patient treated by complete surgical resection followed by radiotherapy and chemotherapy is still alive (+ 5 months). The patient who underwent partial surgical resection followed by radiotherapy and chemotherapy died 7 months later. Two patients treated by radiotherapy alone died, respectively, 2 and 3 months later. After systemic chemotherapy alone, survival times were 1 and 3 months. Conclusions. The prognosis of patients with brain metastases from ovarian carcinoma is poor. A better outcome might be obtained by a multimodal treatment.