Elena Piazza

Pretreatment Quality of Life and Functional Status Assessment Significantly Predict Survival of Elderly Patients With Advanced Non—Small-Cell Lung Cancer Receiving Chemotherapy: A Prognostic Analysis of the Multicenter Italian Lung Cancer in the Elderly Study

PURPOSEnTo study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non-small-cell lung cancer treated with chemotherapy.nnnPATIENTS AND METHODSnData from 566 patients enrolled onto the phase III randomized Multicenter Italian Lung Cancer in the Elderly Study (MILES) study were analyzed. Functional status was measured as activities of daily living (ADL) and instrumental ADL (IADL). The presence of comorbidity was assessed with a checklist of 33 items; items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 (EORTC QLQ-C30) were used to estimate QoL. ADL was dichotomized as none versus one or more dependency. For IADL and QoL, three categories were defined using first and third quartiles as cut points. Comorbidity was summarized using the Charlson scale. Analysis was performed by Cox model, and stratified by treatment arm.nnnRESULTSnBetter values of baseline QoL (P = .0003) and IADL (P = .04) were significantly associated with better prognosis, whereas ADL (P = .44) and Charlson score (P = .66) had no prognostic value. Performance status 2 (P = .006) and a higher number of metastatic sites (P = .02) also predicted shorter overall survival.nnnCONCLUSIONSnPretreatment global QoL and IADL scores, but not ADL and comorbidity, have significant prognostic value for survival of elderly patients with advanced non-small-cell lung cancer who were treated with chemotherapy. Using these scores in clinical practice might improve prognostic prediction for treatment planning.

Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of three randomised trials

BACKGROUNDnChemotherapy is the standard treatment for advanced non-small-cell lung cancer, and myelosuppression is a common side-effect. We aimed to assess whether haematological toxic effects could be a biological measure of drug activity and a marker of efficacy.nnnMETHODSnWe analysed data for 1265 patients who received chemotherapy (vinorelbine, gemcitabine, gemcitabine and vinorelbine, cisplatin and vinorelbine, or cisplatin and gemcitabine) within three randomised trials. Primary landmark analyses were restricted to 436 patients who received all six planned chemotherapy cycles and who were alive 180 days after randomisation. Neutropenia was categorised on the basis of worst WHO grade during chemotherapy: absent (grade 0), mild (grade 1-2), or severe (grade 3-4). All statistical analyses were stratified by treatment allocation. Analyses were repeated in the out-of-landmark group (829 patients), stratifying by treatment allocation and number of chemotherapy cycles. The primary endpoint was overall survival.nnnFINDINGSnIn the landmark group, hazard ratios of death were 0.65 (0.46-0.93) for patients with severe neutropenia and 0.74 (0.56-0.98) for those with mild neutropenia. Median survival after the landmark time of 180 days was 31.4 weeks (95% CI 25.7-39.6) for patients without neutropenia compared with 42.0 weeks (32.7-59.7) for patients with severe neutropenia, and with 43.7 weeks (36.6-66.0) for those with mild neutropenia (severe vs mild vs no neutropenia p=0.0118). Findings were much the same for the out-of-landmark group.nnnINTERPRETATIONnNeutropenia during chemotherapy is associated with increased survival of patients with advanced non-small-cell lung cancer, and its absence might be a result of underdosing. Prospective trials are needed to assess whether drug dosing guided by the occurrence of toxic effects could improve efficacy of standard regimens.

Prevalence and management of pain in Italian patients with advanced non-small-cell lung cancer

Pain is a highly distressing symptom for patients with advanced cancer. WHO analgesic ladder is widely accepted as a guideline for its treatment. Our aim was to describe pain prevalence among patients diagnosed with advanced non-small-cell lung cancer (NSCLC), impact of pain on quality of life (QoL) and adequacy of pain management. Data of 1021 Italian patients enrolled in three randomised trials of chemotherapy for NSCLC were pooled. QoL was assessed by EORTC QLQ-C30 and LC-13. Analgesic consumption during the 3 weeks following QoL assessment was recorded. Adequacy of pain management was evaluated by the Pain Management Index (PMI). Some pain was reported by 74% of patients (42% mild, 24% moderate and 7% severe); 50% stated pain was affecting daily activities (30% a little, 16% quite a bit, 3% very much). Bone metastases strongly affected presence of pain. Mean global QoL linearly decreased from 64.9 to 36.4 from patients without pain to those with severe pain (P<0.001). According to PMI, 616 out of 752 patients reporting pain (82%) received inadequate analgesic treatment. Bone metastases were associated with improved adequacy and worst pain with reduced adequacy at multivariate analysis. In conclusion, pain is common in patients with advanced NSCLC, significantly affects QoL, and is frequently undertreated. We recommend that: (i) pain self-assessment should be part of oncological clinical practice; (ii) pain control should be a primary goal in clinical practice and in clinical trials; (iii) physicians should receive more training in pain management; (iv) analgesic treatment deserves greater attention in protocols of anticancer treatment.

Gemcitabine plus vinorelbine in advanced non-small cell lung cancer: a phase II study of three different doses

Our aim was to study the activity and toxicity of the gemcitabine plus vinorelbine (Gem Vin) combination and to identify the optimal dose. Previously untreated patients aged < 70 years, with stage IV or IIIb (not candidates for radiotherapy) non-small cell lung cancer were eligible. Studied dose-levels of Gem Vin, administered on days 1 and 8 every 3 weeks, were (mg m–2): level I = 1000/25; level II = 1200/25; level III = 1000/30; level IV = 1200/30. A feasibility study was performed at each dose-level, followed by a single-stage phase II study. Dose-level IV was unfeasible because of grade 4 neutropenia. Overall, out of 126 patients enrolled in phase II studies, there were one complete and 32 partial responses (response rate 26%: 95% CI 18–34%). Response rates were 27.9%, 21.4% and 29.3% at levels I, II and III, respectively. The treatment was well tolerated. Toxicity was less frequent and severe at level I. Overall median survival was 33 weeks (95% CI 28–40). Descriptive quality of life analysis showed that patients with a worse baseline global health status score tended to drop out of the study earlier than those with a better score. Gem Vin is feasible at different doses. It is sufficiently active and well tolerated. A phase III study to compare the effect on quality of life of Gem Vin (level I) vs cisplatin-based chemotherapy is ongoing.

Supportive care in patients with advanced non-small-cell lung cancer.

The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patients performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment. Supportive care data were available for 1185 out of 1312 (90%) enrolled patients. Gastrointestinal drugs (45.7%), corticosteroids (33.4%) and analgesics (23.8%) were the most frequently observed categories. The mean number of drugs per patient was 2.43; 538 patients (45.4%) assumed three or more supportive drugs. Vinorelbine does not produce substantial variations in the SC pattern, while cisplatin-based treatment requires an overall higher number of supportive drugs, with higher use of antiemetics (41 vs 27%) and antianaemics (10 vs 4%). Patients with worse PS are more exposed to corticosteroids (42 vs 30%). Elderly patients require drugs against concomitant diseases significantly more than adults (20 vs 7%) and are less frequently exposed to antiemetics (12 vs 27%). In conclusion, polypharmacotherapy is a relevant issue in patients with advanced NSCLC. Chemotherapy does not remarkably affect the pattern of SC, except for some drugs against side effects. Elderly patients assume more drugs for concomitant diseases and receive less antiemetics than adults.

Carboplatin plus vinorelbine plus G-CSF in elderly patients with extensive-stage small-cell lung cancer: a poorly tolerated regimen. Results of a multicentre phase II study

PURPOSE AND METHODSnA multicentre phase II trial (single-stage design) was undertaken to test the activity and toxicity of carboplatin (AUC 5 according to Calvert, day 1) plus vinorelbine (25 mg/m(2) days 1 and 8) with lenograstim support, every 3 weeks in the first line treatment of elderly patients, aged 65 or more, affected by extensive small-cell lung cancer (SCLC). The primary end-point of the trial was the objective response rate. Twenty-three responses among 37 patients were considered necessary to proceed to a phase III trial.nnnRESULTSnTwenty-eight patients were enrolled (median age 70 years). Treatment was remarkably toxic. Three patients died while on treatment. Eleven patients (39.3%, 95% exact confidence interval (CI): 21.5-59.4) had an objective response, that was complete in 2 cases. Median time to progression was 5.1 months (95% CI: 3.3-6.7). Median survival was 7.9 months (95% CI: 4.8-14.4).nnnCONCLUSIONnCarboplatin plus vinorelbine is poorly tolerated and not sufficiently active to warrant phase III comparison with standard chemotherapy regimens in elderly patients with extensive SCLC.

Medical treatment choices for patients affected by advanced NSCLC in routine clinical practice: Results from the Italian observational “SUN” (Survey on the lUng cancer maNagement) study

Lung cancer is the most common cancer in the world today, in terms of both incidence and mortality. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers, and the majority of people diagnosed with NSCLC have locally advanced or metastatic disease. Treatment algorithms have rapidly changed in the last 10 years because of the introduction of new chemotherapeutic and targeted agents in clinical practice. SUN is a 1-year longitudinal observational multicenter study that has consecutively enrolled patients affected by stage IIIB or IV NSCLC with the aim to describe the pattern of care and evolving approaches in the treatment of advanced NSCLC. 987 consecutive NSCLC patients were enrolled between January 2007 and March 2008 at the 74 participating centers throughout Italy and a 12-month follow-up was performed. Cyto-histological diagnosis was performed mainly by broncoscopy with only 24% by CT-scan guided fine-needle aspiration biopsy. 91.4% of the patients received a first-line medical treatment and 8.6% supportive care only. Median age of patients receiving first-line treatment was 66 years. First-line chemotherapy consisted of a single agent in 20% of patients and combination chemotherapy in 80%. The most frequently used chemotherapy regimens were cisplatin plus gemcitabine and carboplatin plus gemcitabine. Median survival of patients receiving first-line chemotherapy was 9.1 months. 32% percent of patients received a second-line treatment that consisted of chemotherapy in 71% of cases and erlotinib in 29%. Overall third-line treatment was given to 7.3% of patients. These results showed a pattern of care for advanced NSCLC that reflects the current clinical practice in Italy at the study time with a high adherence to the International guidelines by the Italian Oncologists.