Capecitabine and Temozolomide in Patients with Advanced Pulmonary Carcinoid Tumours.

BACKGROUND: Temozolomide and capecitabine (CAPTEM) chemotherapy is known to be active in patients with pancreatic neuroendocrine tumours. OBJECTIVE: This retrospective analysis set out to describe the efficacy and toxicity of CAPTEM in patients with advanced pulmonary carcinoids (PCs). METHODS: Patients were included with advanced PC who had been treated with a maximum of 6 cycles of oral temozolomide 200 mg/m2 on days 10-14 and capecitabine 750 mg/m2 b.i.d. on days 1-14, repeated every 28 days, -followed by monthly intramuscular injection of octreotide 30 mg long-acting release as maintenance treatment. RESULTS: Of the 33 patients, all with well-differentiated PC, 61% had atypical carcinoid, 36% had Ki-67 index >10% and 42% had ≥3 organs involved by metastasis. CAPTEM was administered as first-line treatment in 42% of patients, and 17% had received prior somatostatin analogue treatment. Six patients (18%) achieved a partial response, 19 (58%) had stable disease and 8 (24%) developed progressive disease. After a median time of follow-up of 34.8 months, median progression-free survival (PFS) was 9.0 months and median overall survival 30.4 months. Median duration of disease response was 21.7 months and median duration of disease control 9.7 months. Patients with multi-organ metastasis had shorter PFS, but only when treated as second or third line with CAPTEM (p = 0.023). CONCLUSIONS: CAPTEM induced a modest response and PFS rate, comparable to other studies with temozolomide in patients with advanced PC. The efficacy of CAPTEM should be compared to that of monotherapy with temozolomide in a prospective clinical trial.

Predictive factors of thromboembolic complications in patients with esophagogatric adenocarcinoma undergoing preoperative chemotherapy.

BACKGROUND: Thromboembolic events (TEEs) represent a significant treatment and disease complication for cancer patients. In the present study we assessed the incidence of TEEs in patients receiving preoperative chemotherapy for esophagogastric adenocarcinoma. The risk factors for TEE development and their impact on prognosis were further analyzed. MATERIAL AND METHODS: Data from 590 patients with esophagogastric adenocarcinoma, who received preoperative epirubicin-cisplatin with capecitabine (ECX) or 5-fluorouracil (ECF) between 2009 and 2016 in three UK hospitals were retrospectively collected. RESULTS: Twenty-one percent had stomach primary and 98% received ECX chemotherapy. In total, 52 patients (9%) had a venous and 22 (4%) an arterial event. Of those patients with venous TEEs (vTTEs), 39 had pulmonary embolism and 13 deep vein thrombosis, whereas in patients with arterial TEEs (arTTEs), 7 developed a myocardial infarct, 8 developed limb ischemia, 4 developed cerebrovascular accidents and 3 developed superior mesenteric artery thrombosis. ArTEEs were associated with a much higher inoperability rate compared to cases without TEE or with vTEE (77% vs. 20% vs. 31%, respectively, p < .001). Independent risk factors of vTEEs were primary site being the stomach (Odds ratio [OR] 3.24, 95%CI 1.72-6.12, p < .001), being overweight (OR 3.11, 95%CI 1.33-7.26, p = .009) or obese (OR 4.52, 95%CI 1.85-11.09, p = .001) and the presence of central venous access device (OR 3.40, 95%CI 1.00-11.55, p = .050). In contrast, anticoagulant treatment was independently associated with a lower risk of vTEE (OR 0.22, 95%CI 0.06-0.83, p = .026). Khorana score of 4-5 was an independent risk factor of arTEE (OR 6.38, 95%CI 1.85-22.04, p = .003). Finally, arTEEs were an independent poor prognostic factor for OS, when adjusted for baseline patient, tumor and treatment characteristics (Hazard ratio 3.02, 95%CI 1.85-4.95, p < .001). CONCLUSION: Preoperative ECX/ECF chemotherapy for patients with resectable esophagogastric adenocarcinoma was associated with relatively high incidence of TEEs. However, only arTEEs affected patient survival outcomes.

The Role of Continuing Perioperative Chemotherapy Post Surgery in Patients with Esophageal or Gastroesophageal Junction Adenocarcinoma: a Multicenter Cohort Study.

PURPOSE: The aim of this cohort study was to assess the benefit that patients with lower esophageal or gastroesophageal junction (E/GEJ) adenocarcinoma receive by continuing perioperative chemotherapy post-surgery. METHODS: Three hundred twelve patients underwent radical tumor surgical resection after preoperative chemotherapy. Chemotherapy was mainly ECX (epirubicin, cisplatin, capecitabine). Propensity score matching (PSM) was used to compare continuation of chemotherapy post-surgery vs. no postoperative treatment. RESULTS: Two hundred ten patients (67.3%) had GEJ and 102 (32.7%) lower esophageal adenocarcinoma. Microscopically clear surgical margins (R0), according to the Royal College of Pathologists, were achieved in 208 patients (66.7%). In total, 225 patients (72.1%) continued perioperative chemotherapy post-surgery. PSM was used to create two patient groups, well-balanced for basic epidemiological, clinical, and histopathological characteristics. The first included 148 patients who continued perioperative chemotherapy after surgery and the second 86, who did not receive postoperative treatment. The first group had non-significantly different median time-to-relapse (TTR 22.2 vs. 25.7 months, p = 0.627), overall survival (OS 46.1 vs. 36.7 months, p = 0.199), and post-relapse survival (15.3 vs. 8.7 months, p = 0.122). Subgroup analysis showed that only patients with microscopically residual disease after surgery (R1 resection) benefited from continuation of chemotherapy post-surgery for both TTR (hazard ratio [HR] 0.556, 95% CI 0.330-0.936, p = 0.027) and OS (HR 0.530, 95% CI 0.313-0.898, p = 0.018). CONCLUSIONS: Continuation of perioperative chemotherapy post-surgery was not associated with improved outcome in patients with E/GEJ adenocarcinoma. Patients with microscopically residual disease post-surgery might receive a potential benefit from adjuvant chemotherapy.