VITAL phase 2 study: Upfront 5-fluorouracil, mitomycin-C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09-02).

AIM: VITAL, a phase II single-arm study, aimed to evaluate efficacy and safety of panitumumab addition to 5-fluorouracil (5-FU), mitomycin-C (MMC) and radiotherapy (RT) in patients with localized squamous cell carcinoma of the anal canal (SCCAC). METHODS: Adult, treatment-naïve SCCAC patients (Stage T2-T4, any N, M0) and ECOG-PS ≤2, received panitumumab (6 mg/kg, day 1 and Q2W; 8 weeks), 5-FU (1000 mg/m2 /d, days 1-4 and 29-32), MMC (10 mg/m2 , days 1 and 29) and RT 45 Gy (1.8 Gy/fraction) to the primary tumor and mesorectal, iliac and inguinal lymph nodes, plus 10-15 Gy boost dose to the primary tumor and affected lymph nodes. The primary objective was disease free survival rate (DFS) at 3-years (expected 3-year DFS rate: 73.7 ± 12%). RESULTS: Fifty-eight patients (31 women; median age: 59 years; ECOG-PS 0-1:98%; TNM II [29%] (T2 or T3/N0/M0)/IIIA (T1-T3/N1/M0 or T4/N0/M0) [21%]/IIIB (T4/N1/M0 or any T/N2 or N3/M0) [47%]/nonevaluable [4%]) were included. The median follow-up was 45 months. The 3-year DFS rate was 61.1% (95% CI: 47.1, 72.4). The 3-year overall survival rate was 78.4% (95% CI: 65.1, 87.1). Eighteen patients (31.0%) required a colostomy within 2 years posttreatment. Grade 3-4 toxicities were experienced by 53 (91%) patients. Most common grade 3-4 treatment-related events were radiation skin injury (40%) and neutropenia (24%). No toxic deaths occurred. Improved efficacy in colostomy-free survival and complete response rate was observed in human papilloma virus positive patients. CONCLUSIONS: Panitumumab addition to MMC-5FU regimen in SCCAC patients increases toxicity and does not improve patients' outcomes. RT plus MMC-5FU remains the standard of care for localized SCCAC patients.

Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation.

AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team.

Prognostic implications of protein S-100beta serum levels in the clinical outcome of high-risk melanoma patients.

OBJECTIVE: It was the aim of this study to analyze the clinical value of the determination of serum S-100beta protein in high-risk melanoma patients. PATIENTS AND METHODS: Patients were tested for serum S-100beta protein by luminoimmunometric assay after melanoma surgical excision, before starting interferon-alpha2b and every 3 months thereafter, until treatment was completed. RESULTS: Ninety-seven patients were included in the study. Median follow-up was 62.9 months (range 32.7-87.4). High baseline S-100beta levels were associated with positive lymph node status (p = 0.02). High S-100beta levels (during therapy) showed a relation with positive lymph node status (p = 0.014), number of positive lymph nodes (p = 0.01), macroscopic lymph node involvement (p = 0.002) and second melanoma diagnosis at study entry (p = 0.001). By univariate analysis, high baseline S-100beta levels were associated with disease-free survival (p = 0.004) and overall survival (p = 0.0007). Similarly, high S-100beta levels during therapy were associated with disease-free survival (p < 0.0001) and overall survival (p < 0.0001). In the multivariate analysis, high S-100beta levels during therapy (hazard ratio 1.017, 95% CI 1.008-1.026; p < 0.0001) and high baseline S-100beta levels (hazard ratio 3.31, 95% CI 1.10-9.89; p = 0.032) were independent prognostic factors for overall survival when compared with low levels while on therapy and low baseline S-100beta levels, respectively. CONCLUSIONS: These results provide evidence of the clinical usefulness of serum S-100beta level determination in high-risk melanoma patients. S-100beta serum determination should be considered to be included in clinical trials that test adjuvant therapies in melanoma patients.