Elena Collovà

Anticancer oral therapy: Emerging related issues

The use of oral anticancer drugs has shown a steady increase. Most patients prefer anticancer oral therapy to intravenous treatment primarily for the convenience of a home-based therapy, although they require that the efficacy of oral therapy must be equivalent and toxicity not superior than those expected with the intravenous treatment. A better patient compliance, drug tolerability, convenience and possible better efficacy for oral therapy as compared to intravenous emerge as the major reasons to use oral anticancer agents among oncologists. Inter- and intra-individual pharmacokinetic variations in the bioavailability of oral anticancer drugs may be more relevant than for intravenous agents. Compliance is particularly important for oral therapy because it determines the dose-intensity of the treatment and ultimately treatment efficacy and toxicity. Patient stands as the most important determinant of compliance. Possible measures for an active and safe administration of oral therapy include a careful preliminary medical evaluation and selection of patients based on possible barriers to an adequate compliance, pharmacologic issues, patient-focused education, an improvement of the accessibility to healthcare service, as well as the development of home-care nursing symptom-focused interventions. Current evidences show similar quality of life profile between oral and intravenous treatments, although anticancer oral therapy seems to be more convenient in terms of administration and reduced time lost for work or other activities. Regarding cost-effectiveness, current evidences are in favor of oral therapy, mainly due to reduced need of visits and/or day in hospital for the administration of the drug and/or the management of adverse events.

Second-line chemotherapy in malignant pleural mesothelioma: Results of a retrospective multicenter survey

The pemetrexed-cisplatin chemotherapy is standard of care in first-line (FL) treatment of malignant pleural mesothelioma (MPM). The second-line (SL) chemotherapy is considered, but the optimal treatment has not been defined yet. The aim of this study was to evaluate the clinical outcomes of SL-therapy in a series of MPM-patients included in a retrospective multicenter database. Clinical records of MPM-patients who received SL-treatment from 1996 to 2008 were reviewed. Study endpoints were response, overall-survival (OS), and progression-free-survival (PFS) for SL, stratified for patient characteristics, FL-outcomes, and type of SL. Out of 423 patients, 181 with full clinical data were identified. Patients characteristics: median-age 64 years (range: 36-85); male gender 115 (63.5%); good EORTC-score 109 (60.2%); epithelial histology 135 (74.6%). After FL, 147 (81.2%) patients achieved disease-control (DC) and 45 had a time-to-progression≥12 months (TTP≥12). After SL, 95 patients (52.6%) achieved DC (21 response; 74 stable-disease); median PFS and OS were 4.3 and 8.7 months, respectively. According to multivariate analysis, DC after SL-therapy was significantly related to pemetrexed-based treatment (OR: 2.46; p=0.017) and FL-TTP≥12 (OR: 3.50; p=0.006). PFS was related to younger age (<65 years) (HR: 0.70; p=0.045), ECOG-PS0 (HR: 0.67; p=0.022), and FL-TTP≥12 (HR: 0.45; p<0.001). OS was significantly related to ECOG-PS0 (HR: 0.43; p<0.001) and to FL-TTP≥12 (HR: 0.54; p=0.005). In pemetrexed pre-treated patients, re-treatment with a pemetrexed/platinum combination significantly reduced the risk-of-death than pemetrexed alone (HR: 0.11; p<0.001). In conclusion, SL-chemotherapy seems to be active in MPM-patients, particularly in younger patients with ECOG-PS0 and prolonged TTP after FL-pemetrexed-based chemotherapy. In selected patients, re-challenge with pemetrexed-based regimens, preferentially associated with platinum-compound, appears to be an option for SL-setting. Considering the important limitations of this study, due to retrospective nature and the possible selection bias, prospective clinical trials are warranted to clarify these issues.

Natural History of Malignant Bone Disease in Renal Cancer: Final Results of an Italian Bone Metastasis Survey

Background Bone metastasis represents an increasing clinical problem in advanced renal cell carcinoma (RCC) as disease-related survival improves. There are few data on the natural history of bone disease in RCC. Patients and methods Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 398 deceased RCC patients (286 male, 112 female) with evidence of bone metastasis were statistically analyzed. Results Median time to bone metastasis was 25 months for patients without bone metastasis at diagnosis. Median time to diagnosis of bone metastasis by MSKCC risk was 24 months for good, 5 months for intermediate, and 0 months for poor risk. Median number of SREs/patient was one, and 71% of patients experienced at least one SRE. Median times to first, second, and third SRE were 2, 5, and 12 months, respectively. Median survival was 12 months after bone metastasis diagnosis and 10 months after first SRE. Among 181 patients who received zoledronic acid (ZOL), median time to first SRE was significantly prolonged versus control (nu200a=u200a186) (3 months vs 1 month for control; P<0.05). Conclusions RCC patients with bone metastasis are at continuous risk of SREs, and in this survey ZOL effectively reduced this risk.

Bone metastases in patients with metastatic renal cell carcinoma: are they always associated with poor prognosis?

PurposeAim of this study was to investigate for the presence of existing prognostic factors in patients with bone metastases (BMs) from RCC since bone represents an unfavorable site of metastasis for renal cell carcinoma (mRCC).Materials and methodsData of patients with BMs from RCC were retrospectively collected. Age, sex, ECOG-Performance Status (PS), MSKCC group, tumor histology, presence of concomitant metastases to other sites, time from nephrectomy to bone metastases (TTBM, classified into three groups: <1xa0year, between 1 and 5xa0years and >5xa0years) and time from BMs to skeletal-related event (SRE) were included in the Cox analysis to investigate their prognostic relevance.Results470 patients were enrolled in this analysis. In 19 patients (4%),bone was the only metastatic site; 277 patients had concomitant metastases in other sites. Median time to BMs was 16xa0months (range 0u2009−u200944y) with Median OS of 17xa0months. Number of metastatic sites (including bone, pu2009=u20090.01), concomitant metastases, high Fuhrman grade (pu2009<u20090.001) and non-clear cell histology (pu2009=u20090.013) were significantly associated with poor prognosis. Patients with TTBM >5xa0years had longer OS (22xa0months) compared to patients with TTBM <1xa0year (13xa0months) or between 1 and 5xa0years (19xa0months) from nephrectomy (pu2009<u20090.001), no difference was found between these two last groups (pu2009=u20090.18). At multivariate analysis, ECOG-PS, MSKCC group and concomitant lung or lymph node metastases were independent predictors of OS in patients with BMs.ConclusionsOur study suggest that age, ECOG-PS, histology, MSKCC score, TTBM and the presence of concomitant metastases should be considered in order to optimize the management of RCC patients with BMs.

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.

Italian Survey on adjuvant treatment of non-small cell lung cancer (ISA)☆

BACKGROUNDnA recent pooled analysis of randomized trials indicated significant improvement in overall survival from cisplatin-based adjuvant chemotherapy for non-small cell lung cancer (NSCLC), depending on disease stage (only in stages II and III) and PS (≤ 1). Post-operative radiotherapy (RT) is optional for pN2 tumours.nnnPATIENTS AND METHODSnTo evaluate opinions and daily clinical practice of Italian Oncologists about adjuvant treatment of NSCLC, a 46-item questionnaire was delivered via e-mail.nnnRESULTSnSeventy-eight physicians from 68 Centers (out of 98 contacted) returned their questionnaire. Seventy-four, 86, 94, and 78% of them give the indication for adjuvant chemotherapy for stage IIA, IIB, IIIA, and IIIB disease, respectively and 14% in stage IB disease. Stage, PS, and age are taken into consideration evaluating adjuvant approach by 97, 95 and 73%, respectively. Cisplatin-vinorelbine (64%) and cisplatin-gemcitabine (33%), for 4 cycles (81%), are the preferred regimens, while 32% use different regimens. Ninety-two percent indicate RT in pN2 disease and/or positive resection margins. Real Number of patients Needed to Treat (NNT) is probably not completely known/understood and/or used by physicians.nnnCONCLUSIONSnA substantial adherence between clinical daily practice in Italy and scientific progresses is described in this paper, even with some discordances regarding the most appropriate adjuvant chemotherapy regimen.

First-line bevacizumab (B) plus paclitaxel (P) in HER2-negative (HER2-ve) metastatic breast cancer (mBC): Efficacy and safety in an Italian multicenter retrospective study.

e11502 Background: The combination of B with P as first-line treatment for patients (pts) with HER2-ve mBC showed clinical benefits in terms of progression-free survival (PFS) and objective response rate (ORR) without an effect on overall survival (OS). This Italian multicenter retrospective study wanted to evaluate the first-line B plus P in term of efficacy and safety in routine oncology practice.nnnMETHODSnA total of 96 female pts with HER2-ve mBC, Eastern Cooperative Oncology Group performance status of 0 to 1, received B 10 mg/Kg every 2 weeks or 15 mg/Kg every 3 weeks combined with P. PFS and OS were estimated using the Kaplan-Meier method and compared with log-rank test. Chi-square test was employed for comparison of proportion.nnnRESULTSnPts characteristics included: median age 56.8 years; ≥3 sites of lesion 11.5%; previous (neo)adjuvant chemotherapy (CT) 83.4% (taxane-based CT 27.1%). After a median follow-up of 9.6 months, 51 pts progressed and 17 died. 46 pts (48.9% of evaluable pts) attained a disease response: 13 complete responses and 33 partial responses. Median PFS and OS were 9.5 and 22.7 months, respectively. ≥3 sites of lesion were associated with a significant worse PFS (p=0.02) and OS (p=0.03). No associations were found with clinical end-points based on biological variables (ER, Ki-67) stratification. Previous treatment in neo(adjuvant) setting with taxane-based regimens had a significant less chance to obtain disease response (p=0.002), and worse PFS (p=0.009) and OS (p=0.04). The majority of adverse events (AEs) were mild or moderate. Grade ≥3 AEs included hypertension (2.1%), neutropenia (1.0%), thromboembolic events (1.0%) and gastrointestinal perforation (1.0%). The occurrence of hypertension (all grades) was significantly associated with better ORR (76.5% vs 42.8%; p=0.01) and with a trend (not significant) of better PFS (p=0.08).nnnCONCLUSIONSnThe efficacy and safety data of B plus P collected in this study were consistent with results from first-line trials. Pre-treatment in (neo)adjuvant setting with taxane was associated with a worse prognosis. We also confirmed hypertension as significant predictor of B activity.