A randomized phase II study comparing erlotinib versus erlotinib with alternating chemotherapy in relapsed non-small-cell lung cancer patients: the NVALT-10 study.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) administered concurrently with chemotherapy did not improve outcome in non-small-cell lung cancer (NSCLC). However, in preclinical models and early phase noncomparative studies, pharmacodynamic separation of chemotherapy and TKIs did show a synergistic effect. PATIENTS AND METHODS: A randomized phase II study was carried out in patients with advanced NSCLC who had progressed on or following first-line chemotherapy. Erlotinib 150 mg daily (monotherapy) or erlotinib 150 mg during 15 days intercalated with four 21-day cycles docetaxel for squamous (SQ) or pemetrexed for nonsquamous (NSQ) patients was administered (combination therapy). After completion of chemotherapy, erlotinib was continued daily. Primary end point was progression-free survival (PFS). RESULTS: Two hundred and thirty-one patients were randomized, 115 in the monotherapy arm and 116 in the combination arm. The adjusted hazard ratio for PFS was 0.76 [95% confidence interval (CI) 0.58-1.02; P = 0.06], for overall survival (OS) 0.67 (95% CI 0.49-0.91; P = 0.01) favoring the combination arm. This improvement was primarily observed in NSQ subgroup. Common Toxicity Criteria grade 3+ toxic effect occurred in 20% versus 56%, rash in 7% versus 15% and febrile neutropenia in 0% versus 6% in monotherapy and combination therapy, respectively. CONCLUSIONS: PFS was not significantly different between the arms. OS was significantly improved in the combination arm, an effect restricted to NSQ histology. STUDY REGISTRATION NUMBER: NCT00835471.

Practical management of NSCLC patients with long-term bevacizumab treatment: a report of four cases.

INTRODUCTION: Previous research showed that the addition of bevacizumab (a monoclonal antibody against vascular endothelial growth factor [VEGF]) to chemotherapy resulted in a significant efficacy benefit in the treatment of selected patients with advanced nonsquamous non-small cell lung cancer (NSCLC). However, the occurrence and management of adverse events (AEs) during long-term maintenance treatment with bevacizumab is not well known. METHODS: This report presents a descriptive analysis, including the management of AEs, of four patients with advanced NSCLC, who received a relatively long period of bevacizumab maintenance treatment. RESULTS: In patient 1, a 72-year-old retired man with stage cT2N2M1b NSCLC, the only AE related to bevacizumab was a grade 1 rhinorrhea. Treatment resulted in a stable disease, with duration of response of 38 months. Patient 2 had NSCLC stage cT4N3M1b and developed a cavitation and infection after the first cycle of chemotherapy and bevacizumab, which caused a temporary decrease of her quality of life. Bevacizumab therapy resulted in a partial response, with duration of response of 15 months. A 52-year-old female (patient 3) with stage T2bN2M1a NSCLC is currently under treatment and has so far received 42 cycles of maintenance bevacizumab, with stabilized response (duration of response of 29 months) and no noteworthy AEs. The last patient is a 74-year-old male farmer with NSCLC T1N0M1, whose response has lasted for more than 3 years, with until now, no AEs. CONCLUSION: Our retrospective findings of these four patients show the long-term efficacy and safety of bevacizumab treatment in a real-life setting.

Prevention of anaemia by early intervention with once weekly epoetin alfa during chemotherapy.

This study compared the effects of early intervention with standard use of epoetin alfa on haemoglobin (Hb) levels and transfusion requirements in cancer patients receiving chemotherapy. Patients with Hb>10 and < or= 12 g/dL were randomised 1:1 to epoetin alfa (40,000 IU, subcutaneously, once weekly), initiated within 7d of the start of the first on-study chemotherapy cycle (defined as early intervention) versus epoetin alfa when Hb

Autofluorescence bronchoscopy improves staging of radiographically occult lung cancer and has an impact on therapeutic strategy.

BACKGROUND: The ability of conventional CT scans and fiberoptic bronchoscopy to localize and properly stage radiographically occult lung cancer (ROLC) in the major airways is limited. High-resolution CT (HRCT) scanning and autofluorescence bronchoscopy (AFB) may improve the assessment of ROLC before the most appropriate therapy can be considered. PATIENTS AND METHODS: We prospectively studied 23 patients with ROLC, who were referred for intraluminal bronchoscopic treatment (IBT) with curative intent. Additional staging with HRCT and AFB was performed prior to treatment. Twenty patients were men, 9 patients had first primary cancers, and 14 patients had second primary cancers or synchronous cancers. RESULTS: HRCT scanning showed that 19 patients (83%) had no visible tumor or enlarged lymph nodes. With AFB, only 6 of the 19 patients (32%) proved to have tumors < or = 1 cm(2) with visible distal margins. They were treated with IBT. In the remaining 13 patients, abnormal fluorescence indicated more extensive tumor infiltration than could be seen with conventional bronchoscopy alone. Six patients underwent radical surgery for stage T1-2N0 (n = 5) and stage T2N1 (n = 1) tumors. Specimens showed that tumors were indeed more invasive than initially expected. The remaining seven patients technically did not have operable conditions, so they were treated with external irradiation (n = 4) and IBT (n = 3). The range for the time of follow-up for all patients has been 4 to 58 months (median, 40 months). The follow-up data underscore the correlation between accurate tumor staging and survival. CONCLUSIONS: Our data showed that 70% of patients presenting with ROLC had a more advanced cancer than that initially diagnosed, which precludes IBT with curative intent. Additional staging with HRCT and AFB enabled better classification of true occult cancers. Our approach enabled the choice of the most appropriate therapy for each individual patient with ROLC.

Activity of single-agent gemcitabine as second-line treatment after previous chemotherapy or radiotherapy in advanced non-small-cell lung cancer.

The aim of the study was to evaluate activity, toxicity and health-related quality of life (HRQL) with gemcitabine as second-line treatment after previous chemo- or radiotherapy in non-small-cell lung cancer (NSCLC). Patients with previously treated NSCLC were treated with gemcitabine (1000 mg/m(2)) on days 1, 8 and 15 in a 28-day cycle. Eighty patients were included; median age was 57 years (range 38-77). Prior treatment consisted of platinum-containing chemotherapy in 29 patients and high-dose thoracic radiotherapy in 51 patients. Median number of cycles was three (range 1-6). Granulocytopenia CTC grade 3 and 4 occurred in 9% and thrombocytopenia CTC grade 3 and 4 in 9% of cycles. Non-haematological toxicity was mild. Tumour response was achieved in 13% of the patients (95% CI 7-20), median survival time was 26 weeks and 1-year survival was 22%. Tumour response to second-line gemcitabine could not be predicted from response to first-line therapy, first-line treatment modality or treatment interval. In a subset of 35 patients HRQL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-LC13 questionnaires and showed improvement or control of symptoms and functioning in approximately 30% of patients. We conclude that gemcitabine in second-line treatment has modest anti-tumour activity, is well tolerated, and may control tumour-related symptoms and improve HRQL in a significant minority of patients.

[Acute abdomen: consider also the thorax]. / Acute buik: denk ook aan de thorax.

Three patients, 2 men aged 22 and 62 years en 1 woman aged 49, presented with symptoms of an acute abdomen. While infiltrative signs were described on radiodiagnostic images two patients underwent laparotomies. In all three subsequently the diagnosis of pneumonia was established and the patients made full recovery after antibiotic therapy. When a patient presents with symptoms of an acute abdomen, the possibility of an existing pneumonia should always be borne in mind. It is therefore recommended to make a chest radiograph with frontal and lateral view. In the presence of infiltrative signs the existence of pneumonia as the cause of abdominal symptoms should be considered in order to avoid unnecessary laparotomy.