MABp1 as a novel antibody treatment for advanced colorectal cancer: a randomised, double-blind, placebo-controlled, phase 3 study.

BACKGROUND: MABp1, an antibody that targets interleukin 1α, has been associated with antitumour activity and relief of debilitating symptoms in patients with advanced colorectal cancer. We sought to establish the effect of MABp1 with a new primary endpoint in patients with advanced colorectal cancer. METHODS: Eligible patients for the double-blind phase of this ongoing, placebo-controlled, randomised, phase 3 trial, had metastatic or unresectable disease, Eastern Cooperative Oncology Group performance status score 1 or 2, systemic inflammation, weight loss, and other disease-related morbidities associated with poor prognosis, and were refractory to oxaliplatin and irinotecan. Patients were randomly assigned 2:1 to receive either MABp1 or placebo. Randomisation codes were obtained from a centrally held list via an interactive web response system. Patients received an intravenous infusion of 7·5 mg/kg MABp1 or placebo given every 2 weeks for 8 weeks. The primary endpoint was assessed in patients who received at least one dose of MABp1 or placebo (modified intention-to-treat population), and was a composite of stable or increased lean body mass and stability or improvement in two of three symptoms (pain, fatigue, or anorexia) at week 8 compared with baseline measurements. This study is registered with ClinicalTrials.gov, number NCT02138422. FINDINGS: Patients were enrolled between May 20, 2014, and Sept 2, 2015. The double-blind phase of the study was completed on Nov 3, 2015. Of 333 patients randomly assigned treatment, 207 received at least one dose of MABp1 and 102 at least one dose of placebo. 68 (33%) and 19 (19%) patients, respectively, achieved the primary endpoint (relative risk 1·76, 95% CI 1·12-2·77, p=0·0045). The most common grade 3-4 adverse events in the MABp1 group compared with in the placebo group were anaemia (eight [4%] of 207 vs five [5%] of 102 patients), increased concentration of alkaline phosphatase (nine [4%] vs two [2%]), fatigue (six [3%] vs seven [7%]), and increased concentration of aspartate aminotransferase (six [3%] vs two [2%]). After 8 weeks, 17 (8%) patients in the MABp1 group and 11 (11%) in the placebo group had died, but no death was judged to be related to treatment. The incidence of serious adverse events was not significantly different in the MABp1 group and placebo groups (47 [23%] vs 33 [32%], p=0·07). INTERPRETATION: The primary endpoint was a useful means of measuring clinical performance in patients. MABp1 might represent a new standard in the management of advanced colorectal cancer. FUNDING: XBiotech.

Management of symptomatic ascites and post-operative lymphocysts with an easy-to-use, patient-controlled, vascular catheter.

OBJECTIVE: Malignant ascites (MA) can be managed with paracentesis, diuretics, shunt-systems, chemotherapy, and targeted therapies. Some treatments are ineffective; others are associated with complications, involve inpatient procedures, or are not cost-effective. Postoperative lymphocysts (LCs) are managed with inpatient drainage and sclerotherapy or surgery. We tested the use of a vascular catheter in the management of symptomatic MA and LC. METHODS: Fifty-five patients with primary or recurrent cancers with ascites or LCs were managed for symptom relief. A central venous 14-Ga 16-cm catheter (Arrow) was inserted into the abdominal cavity or LC, followed by drainage. RESULTS: The catheter was safely inserted with ultrasound guidance in 43 patients with MA (39 with ovarian cancer: 9 before primary cytoreduction, 30 with recurrence; 4 non-gynecological cancers), and 12 patients with LCs (10 retroperitoneal, 2 bilateral inguinal). All procedures were performed in the outpatient department under local anesthesia, without insertion-related complications. Within a mean of 30 days after catheter placement (range: 7-90 days), no grade 3 infection, peri-drain leakage, or self-removal was noted. In three patients with recurrent ovarian mucinous ascites and one patient with an inguinal LC, some drain obstruction was noted. In cases before primary cytoreduction for ovarian cancer, drainage enabled better nutritional and anesthiological outcomes. Patients with chronic ascites were able to self-monitor the amount of evacuated fluid. Twelve patients whose ascites were drained had chemotherapy at the time, and they reported better well-being, and we estimated better performance status. LC drainage followed by sclerotherapy enabled symptom control and LC radical treatment. CONCLUSION: The use of the vascular catheter is safe, easy, and cost-effective in the management of symptomatic MA and LC.

Clinical practice in febrile neutropenia risk assessment and granulocyte colony-stimulating factor primary prophylaxis of febrile neutropenia in Poland.

AIM OF THE STUDY: The first aim was to investigate the knowledge and awareness of oncologists concerning febrile neutropenia (FN) risk assessment and indications for granulocyte colony-stimulating factor (G-CSF) primary prophylaxis (PP), based on current therapeutic guidelines (PTOK and EORTC). The second aim was to educate the oncologists on best practices for risk assessment and neutropenia management. MATERIAL AND METHODS: The project participants included 169 oncologists from 7 regions working in large specialist oncological centres, university hospitals, regional and city hospitals, specialist outpatient clinics, and oncological wards in small local hospitals. The participants completed a questionnaire based on seven prepared clinical cases of patients with different tumour types and patient characteristics, receiving chemotherapy (CT), and with different levels of FN risk. Participants answered questions related to FN risk assessment and G-CSF use. After completing the questionnaire, the participants proceeded to an educational module in which they were provided with an analysis of correct diagnostic and therapeutic procedures according to the PTOK and EORTC guidelines. RESULTS AND CONCLUSIONS: Febrile neutropenia risk assessment was found to be a routine procedure performed for over 90% of the clinical cases by the participant oncologists. However, the FN risk assessment of clinical cases was correct and consistent with therapeutic guidelines in only 65% of responses. Indications for G-CSF PP were properly identified in 76% of responses and it appeared that indications for G-CSF PP were more likely to be correctly identified in patients receiving high-risk or low-risk regimens than in those receiving intermediate-risk regimens, where the decision to give G-CSF PP is based on additional assessment of patient risk factors. The vast majority of participants who correctly identified the need for PP administered G-CSF in accordance with the dose and schedule recommended by PTOK and EORTC.

Clinical practice in secondary prophylaxis and management of febrile neutropenia in Poland: results of the febrile neutropenia awareness project.

AIM OF THE STUDY: This paper presents the second part of the GoPractice project involving oncologists from seven Polish provinces. The aim of this part of the project was to assess the knowledge of oncologists on indications for granulocyte colony-stimulating factor (G-CSF) secondary prophylaxis (SP) of febrile neutropenia (FN) and FN management based on current therapeutic guidelines (Polish Society of Clinical Oncology [PTOK] and European Organisation for Research and Treatment of Cancer [EORTC]). MATERIAL AND METHODS: The project involved 169 oncologists from 7 regions working in large specialist oncological centers, university hospitals, regional and city hospitals, specialist outpatient clinics and oncological wards in small, local hospitals. The participants completed a questionnaire based on 7 prepared clinical cases of patients with different tumor types and patient characteristics, receiving chemotherapy (CT) with different levels of FN risk. Participants answered questions related to FN risk assessment and G-CSF use as secondary prophylaxis (SP) and for the management of FN. After completing the questionnaire, the participants proceeded to an educational module in which they were provided with an analysis of correct diagnostic and therapeutic procedures according to the PTOK and EORTC guidelines. RESULTS AND CONCLUSIONS: Indications for G-CSF SP were generally well recognized: in nearly 90% of responses, oncologists assessed correctly indications/lack of indications for secondary prophylaxis, in accordance with guideline recommendations and Experts' opinion. However, the use of daily G-CSFs was often recommended by the study participants for the management of FN. This clinical practice is contradictory to PTOK and EORTC recommendations and may unnecessarily increase treatment costs. Changing this clinical approach may be achieved through regular training to improve guideline adherence.

Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non-small-cell lung cancer with high tumour mutational burden: patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial.

BACKGROUND: In the phase III CheckMate 227 study, first-line nivolumab + ipilimumab significantly prolonged progression-free survival (co-primary end-point) versus chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) and high tumour mutational burden (TMB; ≥10 mutations/megabase). AIM: To evaluate patient-reported outcomes (PROs) in this population. METHODS: Disease-related symptoms and general health status were assessed using the validated PRO questionnaires Lung Cancer Symptom Scale (LCSS) and EQ-5D, respectively. LCSS average symptom burden index (ASBI) and three-item global index (3-IGI) and EQ-5D visual analogue scale (VAS) and utility index (UI) scores and changes from baseline were analysed descriptively. Longitudinal changes were assessed by mixed-effect model repeated measures (MMRMs) and time to first deterioration/improvement analyses. RESULTS: In the high TMB population, PRO questionnaire completion rates were ∼90% at baseline and >80% for most on-treatment assessments. During treatment, mean changes from baseline with nivolumab + ipilimumab showed early, clinically meaningful improvements in LCSS ASBI/3-IGI and EQ-5D VAS/UI; with chemotherapy, symptoms and health-related quality of life remained stable (LCSS ASBI/3-IGI, EQ-5D UI) or improved following induction (EQ-5D VAS). MMRM-assessed changes in symptom burden were improved with nivolumab + ipilimumab versus chemotherapy. Symptom deterioration by week 12 was lower with nivolumab + ipilimumab versus chemotherapy (22.3% versus 35.0%; absolute risk reduction: 12.7% [95% confidence interval 2.4-22.5]), irrespective of discontinuation. Time to first deterioration was delayed with nivolumab + ipilimumab versus chemotherapy across LCSS and EQ-5D summary measures. CONCLUSION: First-line nivolumab + ipilimumab demonstrated early, sustained improvements in PROs versus chemotherapy in patients with advanced NSCLC and high TMB. CLINICAL TRIAL REGISTRATION: NCT02477826.

Hodgkin lymphoma of the elderly patients: a retrospective multicenter analysis from the Polish Lymphoma Research Group.

We retrospectively analyzed long-term disease outcome of 350 elderly Hodgkin Lymphoma (eHL) patients treated with ABVD/ABVD-like regimen enrolled in the PLRG-R9 study between 2001 and 2013 in Poland. Complete remission was reported for 73% of early (ES) and 61% advanced stage (AS) patients. Nine (10%) ES and 56 (20%) AS patients have died. With the median follow-up of 36 (1-190) months, 3-year EFS and OS was 0.74 (95%CI: 0.63-0.85) and 0.90 (95%CI: 0.82-0.98) for ES; 0.51 (95%CI: 0.44-0.57), and 0.81 (95%CI: 0.75-0.86) for AS patients, respectively. For ES patients, Cox regression revealed ECOG <2 and age >70 as predictive for inferior OS and EFS. For AS patients, the most predictive for OS was the presence of cardiovascular disorders (CVD) (p = .00044), while for EFS four factors were significantly associated with a poor outcome: ECOG< 2, age >70 years, CVD and extranodal disease. In conclusion, CVD significantly impacts outcomes of ABVD-treated advanced eHL patients.

Cisplatin and carboplatin-based chemotherapy in the first-line treatment of non-small cell lung cancer: Analysis from the European FRAME study.

OBJECTIVES: To explore patient and disease factors, and reasons behind the physician's choice of platinum backbone for the first-line treatment of non-small cell lung cancer (NSCLC), as observed in a European prospective observational study of patients receiving platinum-based chemotherapy as first-line treatment for advanced or metastatic NSCLC (the FRAME study). Additionally, overall survival (OS) for patients who received cisplatin or carboplatin was evaluated. MATERIALS AND METHODS: A post-hoc analysis of the prospective study population was conducted. Baseline characteristics of patients receiving cisplatin versus carboplatin were compared and summarized by propensity score. Survival for matched patients was summarized using the Kaplan-Meier approach. RESULTS: Of the 1564 patients who were included in the prospective study, 1520 received either cisplatin (54%) or carboplatin (46%) in combination with pemetrexed, gemcitabine, taxanes or vinorelbine. Patients treated with carboplatin were older than patients receiving cisplatin (mean age 67 versus 61 years; p<0.001), had poorer performance status (p<0.001), and more comorbidities (p<0.001). Cisplatin was most frequently combined with pemetrexed (47%), and carboplatin most frequently with taxanes (31%). Unadjusted median OS estimates for patients from the total prospective study sample were 11.5 months (95% confidence interval [CI] 10.1-12.9) for cisplatin recipients and 9.0 months (95% CI 8.1-10.6) for carboplatin recipients. Median (95% CI) overall survival for the matched cohorts was 10.8 months (8.8-14.3) for cisplatin versus 9.5 months (8.2-11.3) for carboplatin; p=0.086. CONCLUSION: This post-hoc analysis illustrated real-life differences in patients with NSCLC prescribed platinum-based first-line treatment, and suggested that baseline patient and disease characteristics were associated with physician's choice of platinum agent, with cisplatin being more frequently prescribed to younger and fitter patients.

Non-small cell lung cancer patients with brain metastases treated with first-line platinum-doublet chemotherapy: Analysis from the European FRAME study.

OBJECTIVES: We report on a post-hoc analysis of patients with brain metastases from a large prospective observational study of first-line treatment of non-small cell lung cancer (NSCLC). The aim was to describe baseline characteristics of NSCLC patients with brain metastases, understand their first-line treatment and report outcomes attained in real-world settings. MATERIALS AND METHODS: This post-hoc analysis included all patients in the European observational FRAME study who had brain metastases at initiation of first-line treatment. Descriptive statistics were used for continuous and categorical variables and survival outcomes were assessed using the Kaplan-Meier approach. RESULTS: Our data showed that 17% of patients (263/1564) had spread of the disease to the brain at initiation of first-line treatment. Patients with brain metastases were slightly younger, and more likely to have NSCLC of non-squamous histology than the overall study sample. 34% had received prior palliative radiotherapy to the brain. Our analysis showed a median overall survival (OS) of 7.2 months [95% confidence interval (CI) 6.1-8.2] for all patients with brain metastases treated with first-line platinum-based chemotherapy, ranging from 5.6 months for those treated with gemcitabine plus platinum up to 9.3 months for those treated with pemetrexed plus platinum. Further analysis showed that patients with brain metastases were more frequently treated with pemetrexed platinum-doublet therapy than with any other regimen. CONCLUSIONS: Our analysis provides a unique set of real-world data which adds to current understanding about treatment decisions and outcomes for NSCLC patients with brain metastases for whom there is little clinical trial data available.

Comparison of positron emission tomography/computed tomography with classical contrast-enhanced computed tomography in the initial staging of Hodgkin lymphoma.

We compared initial computed tomography (CT) and positron emission tomography (PET)/CT in 96 patients with Hodgkin lymphoma (HL), assessing the role of baseline PET/CT in stage migration and treatment selection. The number of patients with stage I, II, III and IV disease based on CT versus PET/CT was: 5 vs. 7, 49 vs. 37, 28 vs. 22 and 14 vs. 30, respectively. In 33 (34%) patients, PET/CT changed HL stage: 27 (28%) were upstaged and six (6.3%) downstaged. Upstaging was caused by detection of new extranodal involvements (47 sites in 26 patients): bone marrow (10 patients), spleen (five patients) and lung (two patients). In nine patients≥2 further coexisting locations were detected. Downstaging resulted from the absence of fluorodeoxyglucose (18F-FDG) uptake in enlarged nodes (>15 mm) in the abdomen and pelvis. PET/CT modified HL stage in 34% of patients leading to treatment modification in the majority. Our results indicate that PET/CT should be mandatory in the initial staging of HL.

Outcomes and resource use of non-small cell lung cancer (NSCLC) patients treated with first-line platinum-based chemotherapy across Europe: FRAME prospective observational study.

INTRODUCTION: FRAME was a prospective observational study that captured real-world data on patients with advanced or metastatic non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapies as first-line treatment (FLT) across Europe. As previously reported, most patients observed in the study had initiated FLT with either pemetrexed, gemcitabine, vinorelbine or taxanes in combination with a platinum. Baseline patient and disease characteristics including age, performance status, and histology varied (all p<0.01) across cohorts. METHODS: Consenting adult patients initiating FLT for advanced or metastatic NSCLC with platinum-based chemotherapy, with or without a targeted agent, entered the study between April 2009 and February 2011. The choice of FLT was left to physicians' discretion per routine clinical practice. The primary objective was to evaluate overall survival (OS) across platinum-based doublet chemotherapy cohorts and key secondary objectives included the evaluation of OS in patients with different histological subtypes of NSCLC. Survival outcomes were assessed using Kaplan-Meier analysis, and unadjusted estimates are presented. RESULTS: Median OS in months was 10.3 across cohorts (n=1524), 10.7 for pemetrexed (n=569), 10.0 for gemcitabine (n=360), 9.1 for taxanes (n=295), and 10.7 for vinorelbine (n=300). For patients with non-squamous NSCLC who received cisplatin (n=616, 40% of total), median OS in months was 10.6 across the cohorts, 11.6 for pemetrexed, 8.4 for gemcitabine, 9.6 for taxanes, and 9.9 for vinorelbine. CONCLUSIONS: FRAME describes real-world treatment patterns and survival for patients initiating FLT for advanced or metastatic NSCLC between 2009 and 2011 across Europe.

Influence of histology and biomarkers on first-line treatment of advanced non-small cell lung cancer in routine care setting: baseline results of an observational study (FRAME).

FRAME is a prospective observational study of first-line treatments for advanced non-small cell lung cancer (NSCLC). This interim analysis examines the influence of histology and biomarkers on therapeutic decisions. Baseline characteristic, treatment, and diagnostic procedure data were collected on European patients with stage IIIB/IV NSCLC who were treated with any first-line platinum-based doublet, with or without targeted agents, in routine clinical practice. A total of 1567 patients were observed in 11 countries between April 2009 and February 2011. Patients were mostly non-Asian (96.4%), male (71.5%), smokers (84.4%) with stage IV NSCLC (76.6%) and a performance status of 0-1 (82.2%). Median age was 64 years (range, 33-87). First-line treatments were platinum-based combinations with pemetrexed (36.3%), gemcitabine (23.0%), vinorelbine (19.2%), taxanes (18.9%), or other (2.6%), with concurrent targeted agents in 8.4% of patients (mainly bevacizumab, 7.3%). Diagnosis was based on histology in 70.6%, cytology in 20.3%, and both in 9.1% of patients. The final diagnosis was nonsquamous in 72.2% (including 'not otherwise specified [NOS]' in 11.0%), squamous in 24.4%, and other in 3.4% of patients, with the most common reasons for NOS diagnosis being 'subtyping not technically possible' (42.9%) and 'not important for treatment decision' (40.5%). Only 1.1% (6 patients) in the pemetrexed cohort and 0.9% (1 patient) of patients who received bevacizumab had squamous cell carcinoma. At least one immunohistochemical (IHC) marker was used in 53.5% of patients (thyroid transcription factor-1 [TTF-1]: 47.5%, cytokeratin 7 [CK7]: 38.6%, cytokeratin 5/6 [CK5/6]: 17.9%, p63: 8.8%, cluster of differentiation 56 [CD56]: 4.2%, cytokeratin 14 [CK14]: 1.9%, and other: 24.2%). Testing for additional biomarkers was less common, with the most common being for epidermal growth factor receptor (EGFR) mutation status (26.0%). Physician-reported key factors influencing treatment choice were 'histopathological/cytological diagnosis' (77.4%), 'performance status' (63.2%), and 'age' (52.8%). Similar factors were identified using logistic regression models. Frequent histological testing was observed, likely resulting in few NOS diagnoses. In addition, IHC and predictive biomarkers were routinely assessed. Histology, performance status, and age were key factors influencing first-line treatment choice in the routine care of patients with advanced NSCLC. Clinical Trials. gov registry identifier number: NCT01067794.

The Polish Cancer Anemia Survey (POLCAS): a retrospective multicenter study of 999 cases.

The purpose of the retrospective study in cancer patients in Poland was to analyze the frequency of anemia and methods of its treatment. An attempt was also made to evaluate the hemoglobin (Hb) levels in relation to patient's performance status (PS) prior to and after anticancer treatment. A total of 999 patients (pts) were enrolled, who were followed for up to six chemotherapy cycles or six evaluation points within a 6-month period. The incidence of anemia at the time of enrollment into the study equaled 31%, and was observed mainly among gynecologic and colorectal cancer pts. After anticancer treatment, anemia was reported in 54% of patients, mainly in gynecologic and lung cancer pts. As many as 71% of patients were anemic at some point of time during the survey, which was most often documented among gynecologic, lung and testicular cancer patients. At the 5th visit more than 50% of patients were anemic. The difference between the mean Hb level at 1st and 6th visit was 1.04 g/dL. However, anemia was treated in only 32% of patients (red blood cell transfusions, 61%; iron supplementation, 33%; while erythropoietic, stimulating proteins in just 6%). Worse PS was observed in anemic pts with lung as well as with head and neck cancer. In Poland the occurrence of anemia in cancer patients is as high as 70%. Anemia in this group of patients is underestimated and undertreated. This calls for more attention of physicians providing medical care to cancer patients.

Phase II trial of neoadjuvant therapy with carboplatin, gemcitabine plus thalidomide for stages IIB and III non-small cell lung cancer.

INTRODUCTION: This phase II study assessed the clinical activity of neoadjuvant therapy with carboplatin, gemcitabine, and thalidomide in patients with stage IIB to IIIA non-small cell lung cancer (NSCLC). A secondary goal was to assay a panel of candidate serum biomarkers before and after neoadjuvant therapy. METHODS: Patients received three 21-day cycles consisting of gemcitabine (1000 mg/m) on days 1 and 8, carboplatin (area under the curve, 5.5) on day 1, and thalidomide (200 mg) daily after a gradual dose escalation. RESULTS: A total of 22 patients (12 women, 10 men) were enrolled with inoperable stage IIB NSCLC (32%) or III NSCLC (68%). Median age was 53 years (range: 32-78). Sixty-six cycles of neoadjuvant therapy were administered with 10 cycles requiring dose reductions (21.28%). Response rates were 70% for partial response (n = 14), 20% for disease stability (n = 4), and 10% for disease progression (n = 2). Disease in 14 patients (70%) was downstaged, allowing for 10 lobectomies (45.5%), one bilobectomy (4.5%), and 3 pneumonectomies (13.64%). Grades 3/4 hematologic events included neutropenia (55%), thrombocytopenia (14%), and anemia (14%). Grade 3 skin toxicity was reported in one patient due to thalidomide. Posttreatment increases from baseline in serum levels of angiopoietin (100 pg/ml), platelet/endothelial cell adhesion molecule 1 (100 pg/ml), hepatocyte growth factor (100 pg/ml), vascular endothelial growth factor (10 pg/ml), and interleukin-8 (10 pg/ml) corresponded to a reduction in the probability of death (p = 0.09, 0.055, 0.097, 0.052, and 0.095, respectively). Overall survival was 3.6 years (95% CI: 1.938-infinity). CONCLUSION: This neoadjuvant regimen was well tolerated and effective in inoperable NSCLC and warrants additional investigation.

Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer.

INTRODUCTION: Performance status (PS) 2 patients with non-small cell lung cancer (NSCLC) experience more toxicity, lower response rates, and shorter survival times than healthier patients treated with standard chemotherapy. Paclitaxel poliglumex (PPX), a macromolecule drug conjugate of paclitaxel and polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel and may lead to increased concentrations in tumors due to enhanced vascular permeability. METHODS: Chemotherapy-naive PS 2 patients with advanced NSCLC were randomized to receive carboplatin (area under the curve = 6) and either PPX (210 mg/m/10 min without routine steroid premedication) or paclitaxel (225 mg/m/3 h with standard premedication) every 3 weeks. The primary end point was overall survival. RESULTS: A total of 400 patients were enrolled. Alopecia, arthralgias/myalgias, and cardiac events were significantly less frequent with PPX/carboplatin, whereas grade > or =3 neutropenia and grade 3 neuropathy showed a trend of worsening. There was no significant difference in the incidence of hypersensitivity reactions despite the absence of routine premedication in the PPX arm. Overall survival was similar between treatment arms (hazard ratio, 0.97; log rank p = 0.769). Median and 1-year survival rates were 7.9 months and 31%, for PPX versus 8 months and 31% for paclitaxel. Disease control rates were 64% and 69% for PPX and paclitaxel, respectively. Time to progression was similar: 3.9 months for PPX/carboplatin versus 4.6 months for paclitaxel/carboplatin (p = 0.210). CONCLUSION: PPX/carboplatin failed to provide superior survival compared with paclitaxel/carboplatin in the first-line treatment of PS 2 patients with NSCLC, but the results with respect to progression-free survival and overall survival were comparable and the PPX regimen was more convenient.

Pilot phase II study of gemcitabine and vinorelbine in patients with recurrent or refractory small cell lung cancer.

The aim of this phase II study was to evaluate toxicity, response, time to progression, and overall survival in patients with recurrent or progressive small cell lung cancer (SCLC) receiving the combination of gemcitabine and vinorelbine. This two stages Simon design trial was stopped after 17 patients were enrolled and response rate did not reach a level to justify continuation to the second stage. One patient had received three previous chemotherapy combinations, 5 had two prior chemotherapy regimens, and the remaining 11 had been treated with one prior line of therapy. Their median age was 62 years (35-72). Vinorelbine was administered at 25 mg/m(2) followed by gemcitabine 1000 mg/m(2), on days 1 and 8, every 3 weeks. Sixteen patients were evaluable for toxicity and 11 for response. Grade 3 neutropenia was seen in 5 patients (33%) and 3 patients had grade 4 neutropenia (20%). Three patients had grade 3 thrombocytopenia. No grade 4 non-hematological toxicities were seen. A total of 85 infusions were given, with 1 patient (6%) obtaining a partial response (PR) for a duration of 148 days. Three additional patients had stable disease (19%), but only in 1 patient for longer than 24 weeks. The median time to progression was 47 days for all patients (range 25-196). After a median follow-up of 184 days, 13 patients died (76%). Median overall survival was 164 days. The combination of gemcitabine and vinorelbine has limited activity in relapsed SCLC.

Quantitative assessment of the clavicle radiostructure as a tool for estimation of the osteopathic effect of breast cancer chemotherapy.

Radiological structure (trabeculation) of the clavicle was quantitatively evaluated using the chest X-ray images obtained in 36 pre-menopausal women subjected to CMF (cyclophosphamide, methotrexate, fluorouracil) chemotherapy. For comparison, the values of the quantitative radiostructural indices were estimated from the X-ray images obtained in 65 age-matched pre-menopausal healthy women and 19 post-menopausal women with clinically confirmed osteoporosis. For the analyses, the high-quality routine chest P-A films were used in which the central segment of the clavicle was well visualised. Evaluation of the skeletal radiostructure was carried out using the original software developed by K.W. Zielinski which, in addition to standardising the quality of the image, calculated the structural density as well as the arrangement and mean thickness of the trabeculae. The results demonstrate in a reproducible way that structural density and mean thickness of the clavicular trabeculae were significantly (p < 0.01) lower in pre-menopausal, CMF-treated and post-menopausal, osteoporotic patients than in healthy, control women. Likewise, the relative radiological density of the clavicle was reduced in the former two groups of women as compared to their control counterparts and the difference approached statistical significance. When the X-ray films were compared in each breast cancer patient before and after the chemotherapy the values of all the three parameters were decreased in up to 86% of the treated patients. Overall, the obtained results demonstrate the significant osteopathic side effect of the CMF chemotherapy in pre-menopausal breast cancer patients.