Giovanni Mansueto

Up-front chemotherapy and radiation treatment in newly diagnosed nonsmall cell lung cancer with brain metastases : Survey by outcome research network for evaluation of treatment results in oncology

For patients with stage IV nonsmall cell lung cancer (NSCLC) who present with brain metastasis (BMs), standard platinum‐based chemotherapy regimens have challenged the role of up‐front whole‐brain radiotherapy (WBRT).

Brain metastases from solid tumors: disease outcome according to type of treatment and therapeutic resources of the treating center

BackgroundTo evaluate the therapeutic strategies commonly employed in the clinic for the management of brain metastases (BMs) and to correlate disease outcome with type of treatment and therapeutic resources available at the treating center.MethodsFour Cancer centres participated to the survey. Data were collected through a questionnaire filled in by one physician for each centre.ResultsClinical data regarding 290 cancer patients with BMs from solid tumors were collected. Median age was 59 and 59% of patients had ≤ 3 brain metastases. A local approach (surgery and stereotactic radiosurgery) was adopted in 31% of patients. The local approach demonstrated to be superior in terms of survival compared to the regional/systemic approach (whole brain radiotherapy and chemotherapy, p = <.0001 for survival at 2 years). In the multivariate analysis local treatment was an independent prognostic factor for survival. When patients were divided into 2 groups whether they were treated in centers where local approaches were available or not (group A vs group B respectively, 58% of patients with ≤ 3 BMs in both cohorts), more patients in group A received local strategies although no difference in time to brain progression at 1 year was observed between the two groups of patients.ConclusionsIn clinical practice, local strategies should be integrated in the management of brain metastases. Proper selection of patients who are candidate to local treatments is of crucial importance.

The combination of the selective cyclooxygenase-2 inhibitor celecoxib with weekly paclitaxel is a safe and active second-line therapy for non-small cell lung cancer: a phase II study with biological correlates.

PURPOSEThe selection of effective schedules of treatment for metastatic non-small cell lung cancer still remains a challenge for the oncologist. The present multicentric phase II study was designed in order to investigate the activity and safety of the combination of weekly paclitaxel and celecoxib as second-line treatment for non-small cell lung cancer. As a secondary endpoint, the possible correlation of biomarkers with objective response was investigated in a subset of patients. PATIENTS AND METHODSPatients with platinum-refractory non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0–2 entered the present phase II study. Paclitaxel was administered at the dose of 80 mg/m2 i.v. weekly for 6 weeks, followed by a 2-week rest, and celecoxib, 400 mg p.o. b.i.d. administered continuously. A cycle consisted of 8 weeks of treatment. Determination of circulating vascular endothelial growth factor and interleukin 6 was performed at baseline and every two cycles. RESULTSFifty-eight patients were enrolled: median age, 60 years (range, 30–77 years); male/female ratio = 44/14; performance status, 0, 31 patients; 1, 25 patients; and 2, two patients. Predominant histotype was adenocarcinoma (34 cases), and most patients had at least two sites of disease. According to the intent-to-treat analysis, 14/58 objective responses (24.1%) and 24/58 (41.3%) stabilizations of disease were observed, with a median duration of 4 months (range, 2–22+ months) and 5 months (range, 1–13 months), respectively. Median time to progression and median overall survival were 5 and 11 months, respectively. One-year survival was 42.5%. The main toxicity was neuropathy (4% of grade 3). Preliminary results suggest that decrease in serum vascular endothelial growth factor level is significantly associated with clinical response. DISCUSSIONCombination of celecoxib and weekly paclitaxel is a safe and active new regimen in pretreated non-small cell lung cancer. Toxicity appears not to be worsened by the addition of celecoxib. According to preliminary results, serum vascular endothelial growth factor level seems to be predictive of response, suggesting that it should be further investigated as a surrogate marker of response.

Combination of aprepitant, palonosetron and dexamethasone as antiemetic prophylaxis in lung cancer patients receiving multiple cycles of cisplatin-based chemotherapy

Introduction:  With repeated courses of chemotherapy, chemotherapy‐induced nausea and vomiting (CINV) becomes progressively more difficult to control. The aim of this study was to evaluate whether the antiemetic efficacy of the triple combination aprepitant, palonosetron and dexamethasone could be sustained for up to six cycles of highly emetogenic chemotherapy (HEC) (cisplatin ≥ 50 mg/m2).

Capecitabine versus Bolus Fluorouracil plus Leucovorin (Folinic Acid) as Adjuvant Chemotherapy for Patients with Dukes' C Colon Cancer : Economic Evaluation in an Italian NHS Setting

Background and objective:In the recent X-ACT (Xeloda in Adjuvant Colon cancer Therapy) trial, oral capecitabine (Xeloda®) demonstrated superior efficacy and an improved safety profile compared with infused fluorouracil + leucovorin (folinic acid) [FU+LV] in patients with Dukes’ C colorectal cancer. We used the X-ACT results to determine the cost effectiveness of capecitabine compared with FU+LV from the perspective of the Italian National Health Service (NHS).Methods:Medical resource use data were collected throughout the treatment period. Unit costs for drug administration, hospitalization, emergency room visits and concomitant medications were obtained using Italian published sources. A health-state transition model was used to estimate the incremental cost-effectiveness ratio per quality-adjusted life-month (QALM) gains in the intent-to-treat population (1004 and 983 patients in the capecitabine and FU+LV arms, respectively). Costs and effectiveness were discounted at 3.5%. Costs were calculated in €s (2005 values).Results:Administration of capecitabine required fewer clinic visits per patient than FU+LV (7.35 vs 28.0, respectively). Mean acquisition costs per patient for capecitabine were higher than for FU+LV (€2533 vs €231, respectively), but this difference was offset by the difference in mean chemotherapy administration costs per patient for FU+LV (€4338, compared with €152 for capecitabine). Mean total hospital days and medication costs for treatment-related adverse events were higher for FU+LV than for capecitabine (€352 vs €78, respectively). The cost of emergency room visits for the treatment of adverse events did not differ between the treatment groups. With respect to the lifetime horizon, compared with FU+LV, capecitabine is projected to increase QALMs by a mean 6.5 months, with overall cost savings of €2234 over the treatment period. These findings show that capecitabine is an economically dominant treatment in this setting.Conclusions:Adjuvant capecitabine for patients with Dukes’ C colon cancer has the same activity in terms of outcome when compared with FU+LV but is a lower cost option from the economic perspective of the Italian NHS.

Natural History of Non-Small-Cell Lung Cancer with Bone Metastases

We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59.6% of patients. Skeletal-related events were experienced by 57.7% of patients; the most common was the need for radiotherapy. Median time to first skeletal-related event was 6 months. Median survival after bone metastases diagnosis was 9.5 months and after the first skeletal-related event was 7 months. We created a score based on four factors used to predict the overall survival from the diagnosis of bone metastases: age >65 years, non-adenocarcinoma histology, ECOG Performance Status >2, concomitant presence of visceral metastases at the bone metastases diagnosis. The presence of more than two of these factors is associated with a worse prognosis.This study demonstrates that patients affected by Non-Small Cell Lung Cancer with bone metastases represent a heterogeneous population in terms of risk of skeletal events and survival.

First-line erlotinib and fixed dose-rate gemcitabine for advanced pancreatic cancer

AIM To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer. METHODS We designed a single-arm prospective, multicentre, open-label phase II study to evaluate the combination of erlotinib (100 mg/d, orally) and weekly FDR-Gem (1000 mg/m(2), infused at 10 mg/m(2) per minute) in a population of previously untreated patients with locally advanced, inoperable, or metastatic pancreatic cancer. Primary endpoint was the rate of progression-free survival at 6 mo (PFS-6); secondary endpoints were overall response rate (ORR), response duration, tolerability, overall survival (OS), and clinical benefit. Treatment was not considered to be of further interest if the PFS-6 was < 20% (p0 = 20%), while a PFS-6 > 40% would be of considerable interest (p1 = 40%); with a 5% rejection error (α = 5%) and a power of 80%, 35 fully evaluable patients with metastatic disease were required to be enrolled in order to complete the study. Analysis of prognostic factors for survival was also carried out. RESULTS From May 2007 to September 2009, 46 patients were enrolled (male/female: 25/21; median age: 64 years; median baseline carbohydrate antigen 19-9 (CA 19-9): 897 U/mL; locally advanced/metastatic disease: 5/41). PFS-6 and median PFS were 30.4% and 14 wk (95%CI: 10-19), respectively; 1-year and median OS were 20.2% and 26 wk (95%CI: 8-43). Five patients achieved an objective response (ORR: 10.9%, 95%CI: 1.9-19.9); disease control rate was 56.5% (95%CI: 42.2-70.8); clinical benefit rate was 43.5% (95%CI: 29.1-57.8). CA 19-9 serum levels were decreased by > 25% as compared to baseline in 14/23 evaluable patients (63.6%). Treatment was well-tolerated, with skin rash being the most powerful predictor of both longer PFS (P < 0.0001) and OS (P = 0.01) at multivariate analysis (median OS for patients with or without rash: 42 wk vs 15 wk, respectively, Log-rank P = 0.03). Additional predictors of better outcome were: CA 19-9 reduction, female sex (for PFS), and good performance status (for OS). CONCLUSION Primary study endpoint was not met. However, skin rash strongly predicted erlotinib efficacy, suggesting that a pharmacodynamic-based strategy for patient selection deserves further investigation.

Clinical outcomes in octogenarians treated with docetaxel as first-line chemotherapy for castration-resistant prostate cancer

AIM To assess clinical outcomes in octogenarians treated with docetaxel (DOC) for metastatic castration-resistant prostate cancer. PATIENTS & METHODS The multicenter retrospective study was based on a review of the pre- and post-DOC clinical history, DOC treatment and outcomes. RESULTS We reviewed the records of 123 patients (median age: 82 years) who received DOC every 3 weeks or weekly, without significant grade 3-4 toxicities. Median progression-free survival was 7 months; median overall survival from the start of DOC was 20 months, but post-progression treatments significantly prolonged overall survival. CONCLUSION The findings of this study suggest that toxicity is acceptable, survival is independent of patients age and survival can be significantly prolonged by the use of new agents.

Phase II study of celecoxib and weekly paclitaxel in the treatment of pretreated advanced non-small cell lung cancer (NSCLC)

7337 Background: Cyclooxigenase-2 (COX-2) is overexpressed in about 70% of NSCLC. Selective inhibitors of COX-2 have antitumor activity by blocking angiogenesis and apoptosis. The different mechanisms of action and the non-overlapping side effects suggest their association with cytotoxic agents. This Phase II study was designed to evaluate the activity and tolerability of weekly paclitaxel (PCT) plus celecoxib (CEL), and possible clinical correlations with biomarkers. METHODS PCT was administered at the dose of 80 mg/m2 IV weekly for six weeks followed by two-week rest, and CEL 400 mg p.o. bid continuously. A cycle consisted of 8 weeks. Serum/CTADplasma VEGF and IL-6 analysis was performed at baseline and every two cycles. RESULTS 53 patients (pts), previously treated with front-line platinum-based chemotherapy, entered the trial since January 2002. None of them had previously received taxanes. Pts characteristics: median (m) age 60 yrs (range 30-77); male/female= 43/10; PS 0/1/2= 31/20/2; 30 adenocarcinomas, 14 epidermoid, 1 bronchioloalveolar, 8 undifferentiated NSCLC; most pts had ≥ 2 sites of disease. 43/53 pts completed at least one course of treatment and are assessable for response: 1/43 CR (2.3%), 10/43 PR (23.3%) have been observed, with m duration of 3 mos (range 2-19+); 18/43 pts (41.9%) had stable disease with m duration of 4 mos (range 2-13); m time to progression (TTP) and m overall survival (OS) are 4+ mos and 7+ mos (range 2-23+), respectively. Among the unevaluable pts, six dropped out during the first cycle and the others are too early. Over 100 administered courses, the following toxicity was recorded in all the 53 pts: G4 neutropenia (2); G3 neutropenia (4); G3 anemia (1); G3 neuropathy (3); G3 fatigue (1); G3 alopecia (2). Preliminary results do not suggest any correlation of baseline values of VEGF (m value= 554 and 29.5 pg/mL in serum and CTADplasma, respectively), IL-6 (m value= 3.6 pg/mL) and clinical parameters. Possible modifications of biomarkers after therapy are under evaluation. CONCLUSIONS The combination of CEL and weekly PCT is promising in terms of response rate, TTP and OS in platinum-pretreated NSCLC. No significant financial relationships to disclose.

A case of mesothelioma of the tunica vaginalis testis, with involvement of the pleura and peritoneum.

Mesothelioma is a rare tumor that has increased in incidence in the last decades. It arises most frequently from the lining of the pleural surface, but cases originating in the peritoneum, pericardium and tunica vaginalis testis have been reported in the literature. We report on a case of mesothelioma that originated from the tunica vaginalis testis, involving also the pleura and peritoneum.