Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial.

BACKGROUND: Platinum-based chemoradiation (CCRT) is the standard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma (LAHNSCC). Cetuximab/RT (CET/RT) is an alternative treatment option to CCRT. The efficacy of induction chemotherapy (IC) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in randomized clinical trials. The goals of this phase II-III trial were to assess: (i) the overall survival (OS) of IC versus no-induction (no-IC) and (ii) the Grade 3-4 in-field mucosal toxicity of CCRT versus CET/RT. The present paper focuses on the analysis of efficacy. MATERIALS AND METHODS: Patients with LAHNSCC were randomized to receive concomitant treatment alone [CCRT (Arm A1) or CET/RT (Arm A2)], or three cycles of induction docetaxel/cisplatin/5 fluorouracil (TPF) followed by CCRT (Arm B1) or followed by CET/RT (Arm B2). The superiority hypothesis of OS comparison of IC versus no-IC (Arms B1 + B2 versus A1 + A2) required 204 deaths to detect an absolute 3-year OS difference of 12% (HR 0.675, with 80% power at two-sided 5% significance level). RESULTS: 414 out of 421 patients were finally analyzed: 206 in the IC and 208 in the no-IC arm. Six patients were excluded because of major violation and one because of metastatic disease at diagnosis. With a median follow-up of 44.8 months, OS was significantly higher in the IC arm (HR 0.74; 95% CI 0.56-0.97; P = 0.031). Complete Responses (P = 0.0028), Progression Free Survival (P = 0.013) and the Loco-regional Control (P = 0.036) were also significantly higher in the IC arm. Compliance to concomitant treatments was not affected by induction TPF. CONCLUSIONS: IC followed by concomitant treatment improved the outcome of patients with LAHNSCC without compromising compliance to the concomitant treatments. The degree of the benefit of IC could be different according to the type of the subsequent concomitant strategy. CLINICAL TRIAL NUMBER: NCT01086826, www.clinicaltrials.gov.

Development and daily use of an electronic oncological patient record for the total management of cancer patients: 7 years' experience.

BACKGROUND: We describe our experience with an electronic oncological patient record (EOPR) for the total management of cancer patients. METHODS: The web-based EOPR was developed on the basis of a user-centred design including user education and training, followed by continuous assistance; user acceptance was monitored by means of three questionnaires administered after 2 weeks, 6 months and 6 years. RESULTS: The EOPR has been used daily for all in-ward, day hospital and ambulatory clinical activities since July 2000. The most widely appreciated functions are its rapid multipoint access, the self-updated summary of the patients' clinical course, the management of the entire therapeutic programme synchronised with working agendas and oncological teleconsultation. Security and privacy are assured by means of the separate storage of clinical and demographic data, with access protected by login and a password. The questionnaires highlighted appreciation of rapid data retrieval and exchange and the perception of improved quality of care, but also revealed a sense of additional work and a negative impact on doctor-patient relationships. CONCLUSIONS: Our EOPR has proved to be effective in the total management of cancer patients. Its user-centred design and flexible web technology have been key factors in its successful implementation and daily use.

Immunoreactivity for thyroid transcription factor-1 in stage I non-small cell carcinomas of the lung.

Thyroid transcription factor-1 (TTF-1) is a nuclear protein regulating the transcriptional activity of lung-specific genes in the normal and neoplastic bronchioloalveolar cells. It has been implicated in the normal growth and development of the lung, and the disruption of the TTF-1 locus leads to neonatal death with pulmonary hypoplasia. We evaluated retrospectively the prevalence and clinical significance of TTF-1 immunoreactivity in 222 patients with stage I non-small cell lung carcinoma (NSCLC) with a follow-up time of at least 5 years, and we investigated its relationship with other markers of tumor growth, namely cell proliferation and angiogenesis. TTF-1 immunoreactivity was documented by using the commercially available monoclonal antibody 8G7G3/1 in 72% of 97 adenocarcinomas, 5% of 119 squamous cell carcinomas, and in the glandular component of two adenosquamous carcinomas. Four large cell carcinomas were completely unreactive. In adenocarcinomas, but not squamous cell carcinomas, TTF-1 immunoreactivity correlated significantly with microvessel density (p = 0.04) and inversely with the tumor proliferation fraction assessed by Ki-67 immunostaining (p = 0.03). Also, TTF-1-immunoreactive adenocarcinomas showed a trend for a size less than 3 cm (p = 0.08). TTF-1 expression was not related to specific growth patterns, tumor grade, or tumor cell typing. TTF-1 immunoreactivity did not significantly affect patient survival, although patients with more than 75% immunoreactive neoplastic cells showed a trend for longer overall and disease-free survival. Our findings suggest that TTF-1 could be involved in the development of small pulmonary adenocarcinomas, but it has not prognostic implications in patients with stage I NSCLC.

Persistent excess mortality from lung cancer in patients with stage I non-small-cell lung cancer, disease-free after 5 years.

Among patients with non-small-cell lung cancer (NSCLC), those with pathological stage I have the best expectation of survival; however, survival is reduced to less than 50% in the long term. At present, it is unclear when patients can be reasonably defined as cured, and if they experience a higher incidence of malignant/nonmalignant diseases and a lower expectation of survival than the general population. A total of 134 stage I NSCLC patients, who had undergone resection at the Thoracic Surgery Unit of the General Hospital of Verona (north-eastern Italy) from October 1987 to December 1993, were still disease-free at 5 years. These subjects were further followed up, and morbidity and mortality rates were compared with those recorded in the general population of the same geographical area. The standardised incidence ratios (SIRs) for all malignancies and for lung cancer were higher than expected (2.39, 95% CI=1.6-3.5, P<0.001; 10.1, 95% CI=6.2-15.6, P<0.0001, respectively). The standardised mortality ratio (SMR) was also significantly increased (1.73, 95% CI=1.1-2.6, P=0.013). The excess mortality could be entirely explained by an increase in mortality from lung cancer (5.7, 95% CI=2.8-10.1, P<0.0001). This study shows that patients, resected for pathological stage I NSCLC and tumour-free after 5 years, have a higher incidence of new lung cancer compared with the general population, which in turn determines an excess in all-cause mortality in the following years.

Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as first-line chemotherapy in metastatic breast cancer.

In this phase II, multicentre trial, patients with metastatic breast cancer (MBC) were treated with a combination of gemcitabine, epirubicin and paclitaxel (GET). The primary objective of this study was to determine the tolerability and activity in terms of complete responce (CR) and overall response rate of the GET combination in this patient population. Patients with no prior treatment for MBC, and at least one bidimensionally measurable lesion received gemcitabine 1000 mg m(-2) intravenously (i.v.) over 30 min on days 1 and 4, followed by epirubicin i.v. at 90 mg m(-2) on day 1, and paclitaxel 175 mg m(-2) over 3 h on day 1, every 21 days, up to eight courses. From May 1999 to June 2000, 48 patients were enrolled from seven Italian institutions. A total of 297 chemotherapy courses were administered with a median of six cycles patient(-1) (range 1-8). Seven patients (15%) obtained CR and 27 patients (56%) had partial responce, for an overall response rate of 71% (95% CI: 58.3-83.7). After a median follow-up of 23.7 months (range 7.0-34.4), median progression-free survival was 10.5 months (95% CI: 9.2-11.7), and median overall survival 25.9 months. The main haematological toxicity consisted of grade 3 or 4 neutropenia that occurred in 62% of cycles (22% grade 4 and 40% grade 3). The GET combination is active and well tolerated as first-line chemotherapy for MBC.