Leonidas Apostolidis

Efficacy of topotecan in pretreated metastatic poorly differentiated extrapulmonary neuroendocrine carcinoma

Therapeutic options for metastatic poorly differentiated neuroendocrine carcinoma (NEC) after prior platinum‐based chemotherapy are limited. Topotecan is an approved second‐line chemotherapy for small cell lung cancer (SCLC). NEC is often considered to show a biological behavior similar to SCLC. The aim of this study was to analyze the efficacy of topotecan in pretreated metastatic NEC patients. We performed a retrospective analysis of all patients treated with topotecan for metastatic NEC who presented at our center between January 2005 and December 2014 (n = 30). All 30 patients had received at least a platinum and etoposide containing regimen as prior chemotherapy. Median proliferation rate (Ki67) was 80%. As best response to topotecan five patients showed a stable disease, two patients a partial remission, resulting in a disease control rate of 23%. Of the remaining 23 patients, 14 (47%) showed a progressive disease, nine (30%) died before radiologic response could be evaluated. Median progression‐free (PFS) and overall survival (OS) after start of topotecan was 2.1 and 4.1 months, respectively. In the subgroup analysis, patients with unknown primary (vs. those with a known primary) showed a significantly prolonged PFS of 3.5 months (vs. 1.9, P = 0.0107) and OS of 6.7 months (vs. 2.6 months, P = 0.0168). Grade 3/4 hematotoxicity was observed in 60% of patients. Topotecan shows only moderate antitumor activity in metastatic NEC. Disease control rate is lower than reported for SCLC. However, antitumor activity of topotecan seems higher in patients with unknown primary.

Efficacy and safety of trastuzumab-based therapy in combination with different chemotherapeutic regimens in advanced esophagogastric cancer--a single cancer-center experience.

Background Trastuzumab-based therapy has significantly changed the management of Her-2 positive metastatic esophagogastric cancer. However, only limited experience exists for the management in patients who are not suitable for cisplatin-based therapy. Methods Patients treated with trastuzumab in combination with different chemotherapeutic regimens were analyzed. Response rates, progression-free survival, overall survival, patterns of cardiac toxicity and patterns of maintenance strategies were recorded. Results The response rates, progression-free survival and overall survival in patients with metastatic esophagogastric cancer treated with trastuzumab and different chemotherapeutic regimens compared well with the data published in the TOGA trial. No unexpected toxicity occurred. Different strategies were used for therapy de-escalation. Conclusion Trastuzumab-based therapy is effective in combination with several chemotherapeutic regimens with a safe toxicity pattern. The optimal maintenance strategy remains to be defined.

Early metabolic response in sequential FDG-PET/CT under cetuximab is a predictive marker for clinical response in first-line metastatic colorectal cancer patients: results of the phase II REMOTUX trial

BackgroundTo assess the predictive value of early metabolic response (ΔSUV) after short-term treatment with first-line cetuximab in patients (pts) with RAS-wt metastatic colorectal cancer (mCRC).MethodsIn this prospective phase II study, RAS-wt mCRC pts received a single-agent cetuximab run-in therapy of 2 weeks. ΔSUV was assessed with FDG-PET/CT on days 0 and 14. Early clinical response (ECR) was evaluated with CT on day 56 after treatment with FOLFIRI-cetuximab. Primary endpoint was the predictive significance of ΔSUV for ECR. Secondary endpoints were PFS (progression free survival), OS and the influence of ΔSUV on survival.ResultsForty pts were enroled and 33 pts were evaluable for the primary endpoint. The CT response rate was 57.6%. For responders, ΔSUV was significantly higher (pu2009=u20090.0092). A significant association of ΔSUV with ECR was found (pu2009=u20090.02). Median PFS was 11.7 months and median OS was 33.5 months with a 1-year survival rate of 87.9%. ΔSUV was found to significantly impact the hazard for OS (pu2009=u20090.045).ConclusionsWe demonstrate that cetuximab induces metabolic responses in mCRC pts. The study endpoint was met with the ΔSUV discriminating between responders and non-responders. However, these data should be validated in larger patient cohorts.