Neoadjuvant therapy and transanal endoscopic surgery in T2-T3 superficial, N0, M0 rectal tumors. Local recurrence, complete clinical and pathological response. / Neoadyuvancia y cirugía endoscópica transanal en neoplasias de recto T2-T3 superficial, N0, M0. Recidiva local, respuesta clínica y patológica completa.

INTRODUCTION: The association of preoperative chemoradiotherapy and transanal endoscopic surgery in T2 and superficial T3 rectal cancers presents promising results in selected patients. The main objective is to evaluate the long-term loco-regional and systemic recurrence and, as secondary objectives, to provide results of postoperative morbidity and the correlation between complete clinical and pathological response. METHODS: This is a retrospective observational study including a consecutive series of patients with T2-T3 superficial rectal cancer, N0, M0 who refused radical surgery (2008-2016). The treatment consisted of preoperative chemotherapy (5-fluorouracil or capecitabine) combined with radiotherapy (50, 4Gy) and transanal endoscopic surgery after 8weeks. Preoperative, surgical, pathological and long-term oncologic results were analyzed. RESULTS: Twenty-four patients were included in the study. Two of them required rescue radical surgery for unfavorable pathological results. A local recurrence (4.5%) was observed and 2patients presented systemic recurrence (9%), with a median follow-up of 45 months. A complete clinical tumor response was achieved in 12 patients (50%), and complete pathological tumor response in 9 patients (37.5%). Postoperative complications were observed in 5 patients (20.8%), and they were mild except one. There was no postoperative mortality. CONCLUSIONS: In this stage of rectal cancer, our results seem to support this strategy, mainly when a complete pathological response is achieved. The complete clinical tumor response does not coincide with the pathological tumor response. Randomized prospective studies should be performed to standardize this treatment.

Biweekly cetuximab in combination with FOLFOX-4 in the first-line treatment of wild-type KRAS metastatic colorectal cancer: final results of a phase II, open-label, clinical trial (OPTIMIX-ACROSS Study).

BACKGROUND: This phase II study aims to evaluate the efficacy and safety of biweekly cetuximab in combination with oxaliplatin, leucovorin, and fluorouracil (FOLFOX-4) as first-line treatment of metastatic wild-type KRAS colorectal cancer. METHODS: Previously untreated patients with wild-type KRAS tumours received biweekly cetuximab (500 mg/m2 on day 1) plus FOLFOX-4 (oxaliplatin 85 mg/m2 on day 1, leucovorin 200 mg/m2 on days 1 and 2, and fluorouracil as a 400 mg/m2 bolus followed by a 22-hour 600 mg/m2 infusion on day 1 and 2). Treatment was continued until disease progression, onset of unacceptable toxicities, metastases surgery, or discontinuation request. The primary endpoint was ORR. RESULTS: The intention-to-treat population included 99 patients with a median age of 64.1 years (range, 34-82). The ORR was 60.6% (95% CI, 50.3% to 70.3%). The median follow-up was 17.8 months; the median OS and PFS were 20.8 and 10.1 months, respectively. Metastases from colorectal cancer were surgically resected in 26 (26.3%) patients, with complete resection achieved in 18 (69.2%) patients. Median PFS and OS in patients undergoing metastatic resection were 12.6 and 29.5 months, respectively. The most common grade 3-4 toxicities were neutropenia (32.3%), acne-like rash (15.2%) and diarrhoea (11.1%). CONCLUSIONS: The efficacy of the biweekly combination of cetuximab with FOLFOX-4 in patients with wild-type KRAS tumours supports the administration of cetuximab in a dosing regimen more convenient for patients and healthcare providers. The activity of the biweekly administration is similar to what has been reported for the weekly regimen. Reported toxicity was also consistent with the known toxicity profile of weekly cetuximab. TRIAL REGISTRATION: EudraCT Number 200800690916.

Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study.

BACKGROUND: Somatostatin analogues (SSAs) are indicated to relieve carcinoid syndrome but seem to have antiproliferative effects on neuroendocrine tumours (NETs). This is the first prospective study investigating tumour stabilisation with the long-acting SSA lanreotide Autogel in patients with progressive NETs. METHODS: This was a multicentre, open-label, phase II trial conducted in 17 Spanish specialist centres. Patients with well-differentiated NETs and radiologically confirmed progression within the previous 6 months received lanreotide Autogel, 120 mg every 28 days over ≤92 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, tumour biomarkers, symptom control, quality of life (QoL), and safety. Radiographic imaging was assessed by a blinded central radiologist. RESULTS: Of 30 patients included in the efficacy and safety analyses, 40% had midgut tumours and 27% pancreatic tumours; 63% of tumours were functioning. Median PFS time was 12.9 (95% CI: 7.9, 16.5) months, and most patients achieved disease stabilisation (89%) or partial response (4%). No deterioration in QoL was observed. Nineteen patients (63%) experienced treatment-related adverse events, most frequently diarrhoea and asthenia; only one treatment-related adverse event (aerophagia) was severe. CONCLUSION: Lanreotide Autogel provided effective tumour stabilisation and PFS >12 months in patients with progressive NETs ineligible for surgery or chemotherapy, with a safety profile consistent with the pharmacology of the class. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18.

Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study.

PURPOSE: To assess the activity and toxicity of the combination of gemcitabine plus dacarbazine (DTIC) in patients with advanced soft tissue sarcoma (STS) in a randomized, multicenter, phase II study using DTIC alone as a control arm. PATIENTS AND METHODS: Patients with previously treated advanced STS were randomly assigned to receive either fixed-dose rate gemcitabine (10 mg/m2/min) at 1800 mg/m2 followed by DTIC at 500 mg/m2 every 2 weeks, or DTIC alone at 1200 mg/m2 every 3 weeks. The primary end point of the study was progression-free rate (PFR) at 3 months. RESULTS: From November 2005 to September 2008, 113 patients were included. PFR at 3 months was 56% for gemcitabine plus DTIC versus 37% for DTIC alone (P = .001). Median progression-free survival was 4.2 months versus 2 months (hazard ratio [HR], 0.58; 95% CI, 0.39 to 0.86; P = .005), and median overall survival was 16.8 months versus 8.2 months (HR, 0.56; 95% CI, 0.36 to 0.90; P = .014); both favored the arm of gemcitabine plus DTIC. Gemcitabine plus DTIC was also associated with a higher objective response or higher stable disease rate than was DTIC alone (49% v 25%; P = .009). Severe toxicities were uncommon, and treatment discontinuation for toxicity was rare. Granulocytopenia was the more common serious adverse event, but febrile neutropenia was uncommon. Asthenia, emesis, and stomatitis were the most frequent nonhematologic effects. CONCLUSION: The combination of gemcitabine and DTIC is active and well tolerated in patients with STS, providing in this phase II randomized trial superior progression-free survival and overall survival than DTIC alone. This regimen constitutes a valuable therapeutic alternative for these patients.

[Surgical resection of liver metastases from colorectal carcinoma. Experience in Sant Pau Hospital]. / Resección quirúrgica de metástasis hepáticas de cáncer colorrectal. Experiencia del Hospital de Sant Pau.

INTRODUCTION: Surgical resection is the only available treatment that improves survival in patients with liver metastases from colorectal cancer, particularly when carried out by a multidisciplinary team. MATERIAL AND METHOD: We retrospectively analyzed a consecutive series of 116 patients who underwent 138 liver resections (65.4% minor and 35.5% major) for hepatic metastases from colorectal cancer between 1998 and 2004. In 34.5% of the patients, the lesions were synchronous. All patients were individually assessed by a multidisciplinary team. The mean number of metastases removed per patient was 2.43 (range: 1-10). The mean size of the largest tumor per patient was 40 mm (range: 12-90). In 67.3% of the patients, the primary tumor was at an advanced stage (III-IV). In 98% of the patients, the diagnosis was confirmed by helical computed tomography scans/magnetic resonance imaging and intraoperative ultrasonography. RESULTS: Postoperative morbidity was 31.2% and mortality was 2.2%. A mean of 2.7 units of blood was transfused per patient. Overall 5-year survival was 43.2% (median 50 months). Survival rates varied according to whether the patients had < 4 or > or = 4 colorectal liver metastases (50 and 43 months respectively), tumor size (more or less than 5 cm) (60 and 50.6 months respectively) and whether the site was monolobar or bilobar (60 and 43.11 months respectively). In 16 patients, recurrence of liver metastases led to 22 rehepatectomies. Overall 5-year survival was 36.7% (median 60 months) after the first rehepatectomy but was 36 and 12 months respectively after a second or third rehepatectomy. CONCLUSIONS: These results confirm that multidisciplinary decisions and interventions by specialist liver surgeons, as in our hospital, reduce postoperative morbidity and mortality and increase survival in patients requiring surgical removal of liver metastases from colorectal cancer.