Razvan Popescu

Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06)

BACKGROUND Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer (mCRC) patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after completing first-line chemotherapy. PATIENTS AND METHODS In an open-label, phase III multicentre trial, patients with mCRC without disease progression after 4-6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned to continuing bevacizumab at a standard dose or no treatment. CT scans were done every 6 weeks until disease progression. The primary end point was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significance level of 10% and a statistical power of 85%. RESULTS The intention-to-treat population comprised 262 patients: median follow-up was 36.7 months. The median TTP was 4.1 [95% confidence interval (CI) 3.1-5.4] months for bevacizumab continuation versus 2.9 (95% CI 2.8-3.8) months for no continuation; HR 0.74 (95% CI 0.58-0.96). Non-inferiority could not be demonstrated. The median overall survival was 25.4 months for bevacizumab continuation versus 23.8 months (HR 0.83; 95% CI 0.63-1.1; P = 0.2) for no continuation. Severe adverse events were uncommon in the bevacizumab continuation arm. Costs for bevacizumab continuation were estimated to be ∼30,000 USD per patient. CONCLUSIONS Non-inferiority could not be demonstrated for treatment holidays versus continuing bevacizumab monotheray, after 4-6 months of standard first-line chemotherapy plus bevacizumab. Based on no impact on overall survival and increased treatment costs, bevacizumab as a single agent is of no meaningful therapeutic value. More efficient treatment approaches are needed to maintain control of stabilized disease following induction therapy. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, number NCT00544700.

Multicenter phase II trial of preoperative induction chemotherapy followed by chemoradiation with docetaxel and cisplatin for locally advanced esophageal carcinoma (SAKK 75/02)

BACKGROUND This multicenter phase II study investigated the efficacy and feasibility of preoperative induction chemotherapy followed by chemoradiation and surgery in patients with esophageal carcinoma. PATIENTS AND METHODS Patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the esophagus received induction chemotherapy with cisplatin 75 mg/m(2) and docetaxel (Taxotere) 75 mg/m(2) on days 1 and 22, followed by radiotherapy of 45 Gy (25 x 1.8 Gy) and concurrent chemotherapy comprising cisplatin 25 mg/m(2) and docetaxel 20 mg/m(2) weekly for 5 weeks, followed by surgery. RESULTS Sixty-six patients were enrolled at eleven centers and 57 underwent surgery. R0 resection was achieved in 52 patients. Fifteen patients showed complete, 16 patients nearly complete and 26 patients poor pathological remission. Median overall survival was 36.5 months and median event-free survival was 22.8 months. Squamous cell carcinoma and good pathologically documented response were associated with longer survival. Eighty-two percent of all included patients completed neoadjuvant therapy and survived for 30 days after surgery. Dysphagia and mucositis grade 3/4 were infrequent (<9%) during chemoradiation. Five patients (9%) died due to surgical complications. CONCLUSIONS This neoadjuvant, taxane-containing regimen was efficacious and feasible in patients with locally advanced esophageal cancer in a multicenter, community-based setting and represents a suitable backbone for further investigation.

Intense Therapy in Patients with Locally Advanced Esophageal Cancer beyond Hope for Surgical Cure: A Prospective, Multicenter Phase II Trial of the Swiss Group for Clinical Cancer Research (SAKK 76/02)

Background: There is no standard treatment for patients with locally advanced esophageal carcinoma without systemic metastasis in whom surgery is no longer considered a reasonable option. Patients and Methods: Patients with cervical esophageal tumors, locally very advanced stage (T4 and/or M1a) or locally advanced (T3 and/or N+) with comorbidities were included. Therapy: 2 cycles of induction chemotherapy (cisplatin and docetaxel, both 75 mg/m2 3-weekly) followed by chemoradiation therapy (CRT) comprising a total radiation dose of 59.4 Gy together with docetaxel 15 mg/m2 and cisplatin 25 mg/m2 (5 weekly doses). Primary endpoint: Histologically proven freedom from local failure 6 months after CRT completion. Results: 21 patients were included: 12 had locally very advanced tumors, 3 had cervical esophagus tumors, and 6 were medically unfit for surgery. 18 patients completed therapy per protocol. Grade 3/4 toxicities during CRT were thrombopenia (10%) and dysphagia (15%). 1 patient died due to herpes simplex infection. The primary endpoint was achieved by 4 patients, 6 were alive after median follow-up of 34 months, and median survival was 16 months. Most patients experienced lasting improvement of dysphagia following induction chemotherapy. Conclusions: This regimen is feasible, showed clinically meaningful, long-lasting improvements in quality of life and resulted in long-term survival in 29% of the patients.

Oxaliplatin, Irinotecan and Capecitabine (OCX) for First-Line Treatment of Advanced/Metastatic Colorectal Cancer: A Phase I Trial (SAKK 41/03)

Background: A phase I multicentre trial was conducted to define the recommended dose of capecitabine in combination with oxaliplatin and irinotecan (OCX) in metastatic colorectal cancer. Patients and Methods: Patients with performance status (PS) < 2 and adequate haematological, renal and liver function received oxaliplatin 70 mg/m2 on days 1 and 15, irinotecan 100 mg/m2 on days 8 and 22 and one of five dose levels (DL 1–5, between 800 and 1,600 mg/ m2) of capecitabine on days 1–29 every 5 weeks. Results: 23 patients received a median of 3 cycles. 3 dose-limiting toxicities occurred (DL 1: grade 3 (G3) elevated alkaline phosphatase; DL 5: 1 patient G4 hyperglycaemia/G3 diarrhoea and 1 sudden death). The most common severe adverse event was G3 diarrhoea (13%). Severe haematotoxicity was rare. Therapy was stopped mainly due to metastasectomy or tumour progression (7 patients each). 8 patients reached a partial response. Median time to progression and overall survival (OS) were 8.0 and 21.9 months, respectively. Conclusions: The recommended capecitabine dose in this schedule is 1,400 mg/m2 daily. The OCX regimen is well tolerated. The response rate was surprisingly low with progression-free survival (PFS) and OS within the range of a triple combination. Further studies in combination with targeted agents are warranted.

Quality of Life in Second-Line Treatment of Metastatic Castration-Resistant Prostate Cancer Using Cabazitaxel or Other Therapies After Previous Docetaxel Chemotherapy: Swiss Observational Treatment Registry.

Background The aim was to evaluate quality of life (QoL), pain, and fatigue in patients with metastatic castration‐resistant prostate cancer (mCRPC) treated with different regimens after first‐line docetaxel, as well as disease progression. Patients and Methods Patients with mCRPC having received first‐line chemotherapy with docetaxel were eligible. Second‐line treatment choice was at the discretion of the local investigator. All patients had regular assessments of QoL with the Functional Assessment of Cancer Therapy‐Prostate (FACT‐P) questionnaire, of fatigue with the Brief Fatigue Inventory, and of pain with the McGill Pain Questionnaire‐Short Form. The primary end point was QoL maintenance defined as having a maximum decrease in 2 functional domains of the FACT‐P. Results One hundred thirty‐eight patients were included in 36 oncology centers across Switzerland. QoL analysis was available for all patients (59 who received cabazitaxel; 79 who received other therapy [OT] including 75 who received abiraterone). No significant differences for any of the end points were found between groups. A numerically higher number of patients had QoL maintenance with OT (25 of 79 patients, 32%) compared with cabazitaxel (8 of 59 patients, 14%). QoL improvement was found in 20% of patients (12 of 59) who received cabazitaxel and 24% (19 of 79) who received OT. Mean FACT‐P score did not change in a clinically relevant manner over time in either group. Pain was present in 70% of patients (96 of 138), and a pain response to treatment was noted in 22% (13 of 59) who received cabazitaxel and 29% (23 of 79) who received OT. A similar but minor improvement of fatigue was noted in both groups. Conclusion Some degree of QoL decrease was seen in most patients regardless of second‐line treatment. No significant differences in QoL parameters between cabazitaxel or other second line treatments were found. Micro‐Abstract The aim of the quality of life in second line mCRPC treatment (SEQOND) study was to prospectively evaluate quality of life (QoL) in patients with metastatic castration‐resistant prostate cancer in the second‐line setting, where different treatment options do exist. In this nationwide QoL analysis we could show an improvement of QoL in approximately 20% of patients irrespective of second‐line regimen chosen by the local investigator. No significant differences in QoL parameters between cabazitaxel or other second‐line treatments were found.

Deutsche Osteoonkologische Gesellschaft gegründet

zudem Dr. Holger Uhthoff, Speyer (Schatzmeister) und Prof. Dr. M. Heinrich Seegenschmiedt, Hamburg (Schriftführer) an. Zu Beisitzern wurden PD Dr. Christian Eberhardt, Hanau, Prof. Dr. Tanja Fehm, Tübingen, Prof. Dr. Franz Jakob, Würzburg, und PD Dr. Florian Schütz, Heidelberg berufen. Die Gesellschaft umfasst derzeit 45 Gründungsmitglieder. Mitglied werden kann jeder, der sich wissenschaftlich mit dem Gebiet der Osteoonkologie beschäftigt. Die Gesellschaft wird als Verein eingetragen und die Gemeinnützigkeit wird beantragt.