Autofluorescence bronchoscopy to identify pre-cancerous bronchial lesions

Background. This study aimed to assess the diagnostic yield of autofluorescence bronchoscopy (AFB) in the detection of pre-cancerous bronchial lesions in a non-selected sample of patients. Methods. Both fiberoptic white-light bronchoscopy (WLB) and AFB using the Storz D-light system were performed on 166 consecutive patients. Biopsy specimens were taken in areas of the tracheobronchial tree judged as abnormal or suspicious at WLB and/or AFB. The bronchoscopic procedures were randomly performed by two operators. Results. A total of 93 patients had a positive biopsy specimen: 80 for cancer and 13 for dysplasia. AFB was abnormal or suspicious in 85 of the 93 patients with a sensitivity of 91.4%. Specificity was 50.7%. In 16 patients with normal WLB examination, AFB identified abnormal or suspicious areas which had a positive biopsy. Thus AFB significantly improved sensitivity of WLB (100% vs 82.8%, respectively, p<0.001) in the entire sample of patients studied. Data was further analysed separately for patients with dysplasia and those with cancer. Indeed, 13 of 16 patients recognized only by AFB had a histological diagnosis of dysplasia. The remaining three patients had a diagnosis of cancer (small intraepithelial neoplastic lesions). Since no other patient with dysplasia was found, AFB had a sensitivity of 100% in diagnosing dysplasia. On the other hand, excluding the 13 patients with dysplasia, WLB had a high sensitivity in diagnosing cancer (93.7%). Conclusions. The AFB Storz system showed a high sensitivity. The increase in diagnostic yield of AFB in comparison with WLB was related to the power of AFB to identify pre-cancerous bronchial lesions so showing its usefulness in the early diagnosis of lung cancer

Cetuximab and irinotecan as third-line therapy in advanced colorectal cancer patients: a single centre phase II trial

The epidermal growth factor receptor (EGFR), which participates in signalling pathways that are deregulated in cancer cells, is frequently mutated in colorectal-cancer cells. Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We evaluated the efficacy of cetuximab in weekly combination with irinotecan in metastatic colorectal cancer patients refractory to previous treatments based on oxaliplatin or irinotecan. We included 55 heavily pretreated patients (colon/rectum: 34/11, M/F: 16/29, median age 63 years, range: 27–79) whose disease had progressed during or within an oxaliplatin-based first-line chemotherapy and a irinotecan-based second-line regimen. Patients were followed for tumour response and were also evaluated for the time to tumour progression, and safety of treatment. Cetuximab was given at an initial dose of 400 mg m−2, followed by weekly infusions of 250 mg m−2. Irinotecan was administered weekly at the dose of 90 mg m−2. All patients were assessable for treatment efficacy and safety response rate was 25.4% (95% CI: 21.7–39.6%); 38.2% (95 CI: 18.6–39.8%) of patients showed a disease stability as the best response. As a consequence, the overall tumour control rate was 63.6% (95% CI: 46.4–70.6%). The median time to progression was 4.7 months (95% CI: 2.5–7.1 months) and the median survival time was 9.8 months (95% CI: 3.9–10.1 months). The most common G3-4 noncutaneous side toxicities were: diarrhoea (16.4%), fatigue (12.7%) and stomatitis (7.3%). 89.1% of patients developed skin toxicity and 32.6% of cases was of grade 3–4. No allergic reactions were identified at any courses in any patients. Fever was documented in 27.3% of patients and was most commonly recorded after the first administration. Cetuximab has clinically significant activity even in heavily pretreated colorectal cancer patients progressed after both oxaliplatin and irinotecan-based chemotherapy regimens

Concurrent chemoradiotherapy with low dose weekly gemcitabine in stage III non-small cell lung cancer

BACKGROUND: Combined chemoradiotherapy (CRT) is the treatment of choice for stage III NSCLC. Gemcitabine (G) is a novel deoxycitidine analogue that has been proven to be a potent radiosensitizer. Twenty-two consecutive patients were treated with concurrent CRT to demonstrate the tolerability and efficacy of low dose G given weekly as radiosensitizer in stage III NSCLC. METHODS: Patients with KPS ≥70, adequate bone marrow reserve, with no prior radiotherapy (RT) and surgery were included. Eighteen patients had received prior induction chemotherapy (CT). G (75 mg/m(2)/week) was infused over 1 hour for 6 weeks. Thoracic RT was given two hours later over 6 weeks at 1.8 Gy/day fractions (total dose of 61.2 Gy). Pulmonary toxicity was evaluated with computed tomography scans in 6 weeks. RESULTS: Median age was 60 years (range, 48–75), median follow-up was 15 months (range, 2–40). Sixty-eight percent of patients were male and median KPS score was 90. Conformal 3D-RT planning was used in 64% of patients. G was given for a median of 5 weeks (range 1–9). Twelve patients (54.6%) received all planned CT. G was stopped because of intolerance in 6 and death in 2 patients. Seven patients (31.8%) had radiation pneumonitis. Twenty patients were evaluated for overall response, 1 patient (4.5%) had clinical CR, 81.8% had PR while 9.5% had SD. Median overall survival (OS) was 14 ± 5 months (95% CI 3–25). One- and 2-year OS rates were 55% and 38%. Sixteen patients died of disease-related events (6 with progression of primary tumor, 8 due to metastatic disease), 2 patients died of other causes. One- and 2-year progression-free survival and local control rates were 56%, 27% and 79%, 51%, respectively. CONCLUSION: G might be used as radiosensitizer for patients with stage III NSCLC who could not receive full doses CT with concurrent RT

tAnGo: a randomised phase III trial of gemcitabine in paclitaxel-containing, epirubicin/cyclophosphamide-based, adjuvant chemotherapy for early breast cancer: a prospective pulmonary, cardiac and hepatic function evaluation

tAnGo is a large randomised trial assessing the addition of gemcitabine(G) to paclitaxel(T), following epirubicin(E) and cyclophosphamide(C) in women with invasive higher risk early breast cancer. To assess the safety and tolerability of adding G, a detailed safety substudy was undertaken. A total of 135 patients had cardiac, pulmonary and hepatic function assessed at (i) randomisation, (ii) mid-chemotherapy, (iii) immediately post-chemotherapy and (iv) 6 months post-chemotherapy. Skin toxicity was assessed during radiotherapy. No differences were detected in FEV1 or FVC levels between treatment arms or time points. Diffusion capacity (TLCO) reduced during treatment (P<0.0001), with a significantly lower drop in EC-GT patients (P=0.02). Most of the reduction occurred during EC and recovered by 6-months post treatment. There was no difference in cardiac function between treatment arms. Only 11 patients had echocardiography/MUGA results change from normal to abnormal during treatment, with only five having LVEF<50%. Transient transaminitis occurred in both treatment arms with significantly more in EC-GT patients post-chemotherapy (AST P=0.03, ALT P=0.003), although the majority was low grade. There was no correlation between transaminitis and other toxicities. Both treatment regimens reported temporary reductions in pulmonary functions and transient transaminitis levels. Despite these being greater with EC-GT, both regimens appear well tolerated

Gemcitabine twice weekly as a radiosensitiser for the treatment of brain metastases in patients with carcinoma: a phase I study

Conventional treatment for brain metastases (BM) is whole-brain radiotherapy (WBRT). Efficacy is poor. It might be increased by a potent radiosensitiser such as gemcitabine which is believed to cross the disrupted blood–brain barrier. Primary objective of this study was to determine the maximum tolerated dose (MTD) of twice weekly gemcitabine given concurrently with WBRT. Patients with BM from carcinoma were included. The dose of WBRT was 30 Gys (10 daily fractions). Gemcitabine was given 2–4 h prior to WBRT on days 1 and 8 for the first cohort of patients and then on days 1, 4, 8 and 11. Starting dose was 25 mg m−2, escalated by 12.5 mg m−2 increments. At least three patients were included per level. Dose limiting toxicity (DLT) was defined as grade 4 haematological or grade ⩾3 nonhaematological toxicity. A total of 25 patients were included; 74% had a PS 1 (ECOG). In all, 23 had non-small-cell lung cancer, six colorectal, four breast, two renal cell and one oesophageal carcinoma. A total of 92% had concurrent extracranial disease. Six had single BM, 13 had two or three BM and six multiple. Up to 50 mg m−2 (level 4) no DLT was observed. At 62.5 mg m−2, one out of six patients developed DLT (thrombocytopenia-bleeding). The next dose level (75 mg m−2) was abandoned after grade 4 bone marrow toxicity (fatal neutropenic sepsis) was seen in one out of two patients. So that the dose of 50 mg m−2 will be taken forward for further study

Pemetrexed single agent chemotherapy in previously treated patients with locally advanced or metastatic non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>The main objective of this study was to evaluate the safety of second-line pemetrexed in Stage IIIB or IV NSCLC.</p> <p>Methods</p> <p>Overall, 95 patients received pemetrexed 500 mg/m²i.v. over Day 1 of a 21-day cycle. Patients also received oral dexamethasone, oral folic acid and i.m. vitamin B12 supplementation to reduce toxicity. NCI CTC 2.0 was used to rate toxicity. All the adverse events were graded in terms of severity and relation to study treatment. Dose was reduced in case of toxicity and treatment was delayed for up to 42 days from Day 1 of any cycle to allow recovering from study drug-related toxicities. Tumor response was measured using the RECIST criteria.</p> <p>Results</p> <p>Patients received a median number of 4 cycles and 97.8% of the planned dose. Overall, 75 patients (78.9% of treated) reported at least one adverse event: 34 (35.8%) had grade 3 as worst grade and only 5 (5.2%) had grade 4. Drug-related events occurred in 57.9% of patients. Neutropenia (8.4%) and leukopenia (6.3 %) were the most common grade 3/4 hematological toxicities. Grade 3 anemia and thrombocytopenia were reported in 3.2% and 2.1% of patients, respectively. Diarrhea (6.3%), fatigue (3.2%) and dyspnea (3.2%) were the most common grade 3/4 non-hematological toxicities. The most common drug-related toxicities (any grade) were pyrexia (11.6%), vomiting, nausea, diarrhea and asthenia (9.5%) and fatigue (8.4%). Tumor Response Rate (CR/PR) in treated patients was 9.2%. The survival at 4.5 months (median follow-up) was 79% and the median PFS was 3.1 months. Twenty patients (21.1%) died mainly because of disease progression.</p> <p>Conclusion</p> <p>Patients with locally advanced or metastatic NSCLC could benefit from second-line pemetrexed, with a low incidence of hematological and non-hematological toxicities.</p

Concurrent administration of Docetaxel and Stealth® liposomal doxorubicin with radiotherapy in non-small cell lung cancer : excellent tolerance using subcutaneous amifostine for cytoprotection

The substantial augmentation of the radiation sequelae during chemo–radiotherapy with novel drugs masks the real potential of such regimens. In this study we examined whether subcutaneous administration of amifostine can reduce the toxicity of a highly aggressive chemo–radiotherapy scheme with Stealth® liposomal doxorubicin (Caelyx®) and Docetaxel (Taxotere®) in non-small cell lung cancer. Twenty-five patients with stage IIIb non-small cell lung cancer were recruited in a phase I/II dose escalation trial. The starting dose of Taxotere® was 20 mg m−2 week and of Caelyx® was 15 mg m−2 every two weeks, during conventionally fractionated radiotherapy (total dose of 64 Gy). The dose of Taxotere®/Caelyx® was, thereafter, increased to 20/25 (five patients) and 30/25 mg m−2 (15 patients). Amifostine 500 mg was given subcutaneously before each radiotherapy fraction, while an i.v. amifostine dose of 1000 mg preceded the infusion of docetaxel. The ‘in-field’ radiation toxicity was low. Grade 3 esophagitis occurred in 9 out of 25 (36%) patients. Apart from a marked reduction of the lymphocyte counts, the regimen was deprived from any haematological toxicity higher than grade 1. No other systemic toxicity was noted. The CR and CR/PR rates in 15 patients treated at the highest dose level was 40% (6 out of 15) and 87% (13 out of 15) respectively. It is concluded that the subcutaneous administration of amifostine during high dose Taxotere®/Caelyx® chemo–radiotherapy is a simple and effective way to render this aggressive regimen perfectly well tolerated, by reducing the systemic and the ‘in-field’ toxicity to the levels expected from simple conventional radiotherapy. The impressive tolerance and the high CR rate obtained encourages the conduct of a relevant randomized trial to assess an eventual survival benefit in patients with non-small cell lung cancer

Impact of gastrointestinal side effects on patients’ reported quality of life trajectories after radiotherapy for prostate cancer: Data from the prospective, observational pros-it CNR study

Radiotherapy (RT) represents an important therapeutic option for the treatment of localized prostate cancer. The aim of the current study is to examine trajectories in patients’ reported quality of life (QoL) aspects related to bowel function and bother, considering data from the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study, analyzed with growth mixture models. Data for patients who underwent RT, either associated or not associated with androgen deprivation therapy, were considered. QoL outcomes were assessed over a 2-year period from the diagnosis, using the Italian version of the University of California Los Angeles-Prostate Cancer Index (Italian-UCLA-PCI). Three trajectories were identified for the bowel function; having three or more comorbidities and the use of 3D-CRT technique for RT were associated with the worst trajectory (OR = 3.80, 95% CI 2.04–7.08; OR = 2.17, 95% CI 1.22–3.87, respectively). Two trajectories were identified for the bowel bother scores; diabetes and the non-Image guided RT method were associated with being in the worst bowel bother trajectory group (OR = 1.69, 95% CI 1.06–2.67; OR = 2.57, 95% CI 1.70–3.86, respectively). The findings from this study suggest that the absence of comorbidities and the use of intensity modulated RT techniques with image guidance are related with a better tolerance to RT in terms of bowel side effects

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care