V. Mutri

Phase II study of cetuximab in combination with cisplatin and docetaxel in patients with untreated advanced gastric or gastro-oesophageal junction adenocarcinoma (DOCETUX study)

Background:The conventional treatment options for advanced gastric patients remain unsatisfactory in terms of response rate, response duration, toxicity, and overall survival benefit. The purpose of this phase II study was to evaluate the activity and safety of cetuximab combined with cisplatin and docetaxel as a first-line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma.Methods:Untreated patients with histologically confirmed advanced gastric or gastro-oesophageal adenocarcinoma received cetuximab at an initial dose of 400 mg m−2 i.v. followed by weekly doses of 250 mg m−2, cisplatin 75 mg m−2 i.v. on day 1, docetaxel 75 mg m−2 i.v. on day 1, every 3 weeks, for a maximum of 6 cycles, and then cetuximab maintenance treatment was allowed in patients with a complete response, partial response, or stable disease.Results:Seventy-two patients (stomach 81.9% and gastro-oesophageal junction 18.1%; locally advanced disease 4.2%; and metastatic disease 95.8%) were enrolled. The ORR was 41.2% (95% CI, 29.5–52.9). Median time to progression was 5 months (95% CI, 3.7–5.4). Median survival time was 9 months (95% CI, 7–11). The most frequent grades 3–4 toxicity was neutropenia (44.4%). No toxic death was observed.Conclusions:The addition of cetuximab to the cisplatin/docetaxel regimen improved the ORR of the cisplatin/docetaxel doublet in the first-line treatment of advanced gastric and gastro-oesophageal junction adenocarcinoma, but this combination did not improve the TTP and OS. The toxicity of cisplatin/docetaxel chemotherapy was not affected by the addition of cetuximab.

Does Stent Placement for Advanced Colon Cancer Increase the Risk of Perforation During Bevacizumab-Based Therapy?

BACKGROUND & AIMS Data on the safety of bevacizumab-based therapies for patients carrying a self-expandable metallic stent (SEMS) for occlusive colon cancer are lacking. We report 2 cases of colon perforation observed in our case series of patients with SEMS for occlusive colon cancer. METHODS Patients with occlusive symptoms caused by colon cancer received a colonic stent under endoscopic and radiologic guidance. RESULTS Over a 10-month period, 28 patients with occlusive colon cancer were treated with stent placement. The stent was placed as a bridge to surgery in 12 patients who were treated surgically within 4 to 78 days after the endoscopic procedures, without any stent-related complications. Seven patients did not receive any other antitumor treatment as a result of concomitant comorbidities. Nine patients with both primary tumor and metastatic lesions were treated with medical therapy. Over a median follow-up period of 131 days colonic perforation occurred in the 2 patients treated with a combination of capecitabine and oxaliplatin plus bevacizumab. CONCLUSIONS Further studies are needed to clarify whether SEMS placement increases the risk of perforation caused by bevacizumab-based therapies.

Cancer chemotherapy near the end of life: the time has come to set guidelines for its appropriate use.

Aims and Background This study retrospectively analyzes the use of chemotherapy in patients who died of advanced cancer either after having been in care at the Medical Oncology Unit (MOU) of the University Hospital of Bologna, Italy, or after having been assisted in their terminal disease phase by the Bologna Oncological Hospice at Home (OHH) of the Associazione Nazionale Tumori (ANT) Italia Foundation. In the latter group, the prescription and delivery of chemotherapy had been performed by doctors of medical oncology departments other than the MOU. Results Between January 2003 and September 2005, 793 deaths of patients were recorded (MOU: 312; OHH: 481). At least one cycle of chemotherapy had been received by 445 patients (56.1%). The most common cancer types were lung cancer (26.7%), colorectal cancer (14.8%), and breast cancer (11.2%). At the time of the last chemotherapy (l-CT), the median age of the patients was 68 years (range, 22–98 years) and the median KPS was 70 (range, 40–100). The median interval between l-CT and death was 71 days (range, 1-1913 days). One hundred and one patients (22.7%) had received their l-CT in the last 30 days of their life, 86% of them having intermediately chemosensitive (71%) or chemoresistant (14%) tumors. The l-CT in the last month of life was first line in 56% of cases and consisted of costly new-generation drugs in 36.6% of cases. Conclusions The study suggests the urgent need to lay down guidelines for the appropriate use of chemotherapy in advanced cancer patients with a short life expectancy.

The predictive value of 18F-FDG-PET early evaluation in patients with metastatic gastric adenocarcinoma treated with chemotherapy plus cetuximab

BackgroundThe aim of the study was to evaluate whether the therapy-induced reduction of the 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) maximum standardized uptake value in patients with advanced gastric adenocarcinoma treated with chemotherapy plus cetuximab could predict the objective response and outcome early during the treatment.MethodsThe study was performed as a part of a phase II trial evaluating cetuximab plus the leucovorin/5-fluorouracil/irinotecan (FOLFIRI) regimen. The objective response was evaluated according to the response evaluation criteria in solid tumors (RECIST) every 6 weeks. The early metabolic response evaluated by 18F-FDG-PET was assessed according to our own evaluated cutoff value (<35%) after receiver operating characteristic (ROC) analysis.ResultsTwenty of 22 patients had positive baseline 18F-FDG-PET. The best RECIST response was: complete response (CR), 3; partial response (PR), 9; stable disease (SD), 8. Twelve patients (60%) were classified as metabolic responders and 8 (40%) as nonresponders. At the median follow-up time of 11 months, median time to disease progression (TTP) and overall survival (OS) for early metabolic responders versus nonresponders were 11 versus 5 months (P = 0.0016) and 16 versus 6 months (P = 0.1493), respectively.ConclusionThe early metabolic response evaluated by 18F-FDG-PET predicted the clinical outcome in this series of patients with advanced gastric cancer treated with chemotherapy plus cetuximab.

Expert opinions of the first Italian Consensus Conference on the management of malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a very important public health issue. A large amount of data indicates a relationship between mesothelioma and asbestos exposure. The incidence has both considerably and constantly increased over the past 2 decades in the industrialized countries and is expected to peak in 2010–2020. In Italy, a standardized-rate incidence in 2002 among men was 2.98 per 100,000 and 0.98 per 100,000 among women, with wide differences from one region to another. Stage diagnosis and definition may be difficult. Management of patients with MPM remains complex, so an optimal treatment strategy has not yet been clearly defined. The First Italian Consensus Conference on Malignant Pleural Mesothelioma was held Bologna (Italy) in May 20, 2008. The Consensus Conference was given the patronage of the Italian scientific societies AIOM, AIRO, AIPO, SIC, SICO, SICT, SIAPEC-IAP, AIOT, GOAM, and GIME. This Consensus did not answer all of the unresolved questions in MPM management, but the Expert Opinions have nonetheless provided recommendations, presented in this report, on MPM management for clinicians and patients.

Impact of intervention aimed at improving the integration of oncology units and local palliative care services: results of the multicentre prospective sequential MIRTO study

Background Chemotherapy (CT) in patients with advanced cancer (ACP) near the end of life is an increasing practice of oncology units. A closer integration with palliative care (PC) services could reduce the use of potentially harmful CT. This prospective study is aimed at assessing whether a more integrated care model could reduce CT use near the end of life and increase local PC service utilisation. Methods The study enrolled sequentially two cohorts of ACP with an estimated life expectancy of ≤6 months. In the first cohort, the usual oncologist’s practice to prescribe CT and to activate local PC services were recorded. In cohort 2, the oncologist’s decision was taken after an in-hospital consultation with the local PC teams. After patient death, a follow-back survey was carried out. Results The two cohorts included 109 and 125 evaluable patients, respectively. The oncologist’s decision to prescribe CT occurred in 51.4% and 60%, respectively: the percentages of patients receiving the final CT administration in the last 30 days of life did not differ in the two cohorts (33.9% and 29.3%, respectively,p=0.83). Conversely, an increase in home PC service utilisation (from 56.9% to 82.4%, p=0.00), at home deaths (from 40.4% to 56.8%, p=0.01) and in-hospice deaths (from 8.3% to 19.2%, p=0.00) occurred in cohort 2. Conclusion The implementation of an initial in-hospital consultation of oncologists and experienced home PC teams has not reduced the use of CT near the end of life but increased PC service utilisation and reduced in-hospital deaths.