[Show abstract][Hide abstract] ABSTRACT: Most patients with non-small-cell lung cancer (NSCLC) are elderly but evidence to guide appropriate treatment decisions for this age group is generally scant. Careful evaluation of the elderly should be undertaken to ensure that treatment appropriate for the stage of the tumour is guided by patient characteristics and not by age. The Comprehensive Geriatric Assessment (CGA) remains the preferred option, but briefer tools may be appropriate to select patients for further evaluation. The predicted outcome should be used to guide management decisions together with a reappraisal of polypharmacy. Patient expectations should also be taken into account. Management recommendations are generally similar to those of general guidelines for the NSCLC population, although the risks of surgery and toxicity of chemotherapy and radiotherapy are often increased in the elderly compared with younger patients; therefore, patients should be closely scrutinised and subjected to a CGA to ensure suitability of the planned treatment. If surgery is indicated, then lobectomy is generally the preferred option, although limited resection may be more feasible for some. Radiotherapy with curative intent is an alternative, with stereotactic body radiotherapy the most likely preferred modality. Adjuvant chemotherapy is also an appropriate approach, whereas adjuvant radiotherapy is generally not recommended. Concurrent chemoradiotherapy should be considered for elderly patients with inoperable locally advanced disease and chemotherapy for advanced/metastatic disease. Efforts should also be made to increase participation of elderly patients with NSCLC in clinical trials, thereby enhancing evidence-based treatment decisions for this majority group. This will require overcoming barriers relating to trial design and to physician and patient awareness and attitudes.
Annals of Oncology 07/2014; 26(3). DOI:10.1093/annonc/mdu268 · 7.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate systemic exposure to carboplatin and its haematological toxicity in patients with advanced non-small cell lung cancer both older and younger than 70 years when the target area under the curve (AUC) in elderly patients was reduced by 20%. For this purpose, a population pharmacokinetic model was developed and the haematological toxicity of the drug was assessed. A total of 33 patients received carboplatin on day 1 and gemcitabine (1250 mg/m(2) ) on days 1 and 8. This schedule was repeated every 21 days. The Calvert-Crokcoft-Gault formula was employed to calculate a dose of carboplatin with a target AUC of 5 mg/min./mL in patients under 70 years and 4 mg/min./mL in patients aged 70 or older. The data of 24 patients were treated for population modelling performed with the nonmem (University of California, San Francisco, CA, USA) approach. Haematological toxicity was evaluated for all 33 patients enrolled in the study. The carboplatin systemic exposure measured by the AUC (mg/min./mL) was 5.98 (5.45; 6.51) and 5.36 (5.02; 5.69) for the younger patients and older groups, respectively. No significant differences were observed between the two groups with respect to rates of grade 3+ anaemia, neutropenia or thrombocytopenia. In clinical practice, a target AUC of 4 mg/min./mL carboplatin is applied to patients aged 70 and over, but the actual systemic exposure to the drug is higher. This supports a target AUC of 4 mg/min./mL carboplatin for patients older than 70 years when the dose is calculated by means of the Calvert-Crokcoft-Gault formula.
[Show abstract][Hide abstract] ABSTRACT: New therapeutic approaches are being developed based on the findings that several genetic abnormalities underlying NSCLC could influence chemosensitivity. In this study, we assessed whether the presence of polymorphisms in ERCC1, XPD, RRM1 and MDR1 genes can affect the efficacy and the tolerability of cisplatin and vinorelbine in NSCLC patients.
Eligible patients had histological confirmed stage IV or IIIB (with malignant pleural effusion) non-small-cell lung cancer (NSCLC) previously untreated with chemotherapy; World Health Organization performance status (PS) 0-1. Patients received intravenous doses of vinorelbine 25 mg/m² on day 1 and 8 and cisplatin 75 mg/m² on day 1, every 21 days, for a maximum of eight cycles.
94 patients were included. Median age was 61 years; 84% were male; WHO performance status (PS) was 0 in 24%; and 88% of patients had stage IV disease. The median number of cycles was 6. Overall median survival was 10.92 months (95% CI 9.0-12.9). Overall median time to progression was 5.89 months (95% CI 5.2-6.6). Results of the multivariate analysis for time to progression showed that ECOG 0 (hazard ratio [HR] ECOG 1 vs. ECOG 0, 1.74; p=0.036), MDR13435CC (HR CT vs. CC, 2.01; p=0.017; HR TT vs. CC, 1.54; p=0.22), and decreasing age (HR of age, 0.97; p=0.016) were the most powerful prognostic factors significantly related to lower risk of progression. Whereas ECOG 0 was the only prognostic factor for survival (HR ECOG 1 vs. ECOG 0, 3.02; p=0.001). There was no significant association between any of the SNPs analysed and the occurrence of vinorelbine and cisplatin-related toxicity.
In our results, the most important prognostic factors associated with lower risk of progression were MDR1 3435 CC genotype, PS 0 and younger age.
[Show abstract][Hide abstract] ABSTRACT: Healthy elderly patients with metastatic colorectal cancer may benefit from chemotherapy as much as the younger population. This analysis compares the outcomes of first-line oxaliplatin plus fluoropyrimidines in elderly versus young patients.
348 patients were randomized to capecitabine 1000 mg/(m2 12 h), days 1-14 plus oxaliplatin 130 mg/m2 day 1, every 3 weeks or weekly infusional 5-FU 2250 mg/m2 over 48 h plus bimonthly oxaliplatin 85 mg/m2. We evaluated response rate, time to progression, overall survival and toxicity according to age.
ORR for elderly and young patients were 34.9% and 44.7%, respectively (p=0.081). Median TTP did not differ between the two groups: 8.3 months for patients > or =70 years and 9.6 months for those <70 years (p=0.114). Median OS was 16.8 months and 20.5 months for the > or =70 and <70 years groups, respectively (p=0.74). With XELOX, mild paresthesia and an increase in transaminase levels were more frequent for young patients, whereas grade 3/4 diarrhea was higher in those > or =70 years (25% vs. 8%, p=0.005). For FUOX, only paresthesia was significantly lower in patients > or =70 years (53% vs. 71%, p=0.032).
Elderly patients with MCRC benefit from first-line oxaliplatin-fluoropyrimidine combinations as much as younger patients, without increased toxicity.
[Show abstract][Hide abstract] ABSTRACT: We studied the role of TS (5'VNTR, 5'SNP and 3'UTR), XRCC1-399, XPD-751, ERCC1-118 and XRCC3-241 genetic polymorphisms in tailoring fluroropyrimidine/oxaliplatin treatment. For this purpose, 110 XELOX (capecitabine/oxaliplatin)- or FUOX (fluorouracil/oxaliplatin)-treated metastatic colorectal cancer patients were selected prospectively for genotyping. In the FUOX group, TS-3'UTR +6bp/+6bp (hazards ratio, HR=2.62, p=0.007) and ERCC1-118C/T or C/C (HR=1.96, p=0.050) genotypes correlated with a shorter progression-free survival (PFS). When analysed jointly, the higher the number of favourable genotypes (FG) the longer the PFS (6.8m, 9.6m and 25.8m for 0, 1 or 2 FG; p=0.005). Disease-control rate was 100% in patients with 2 FG (87% and 38.5% for 1 or 0 FG; p=0.001). In the multivariate analysis, ERCC1-118 (HR=2.12, p=0.0037) and TS-3'UTR (HR=2.68, p=0.006) were strong independent prognostic factors. According to this, patients harbouring TS-3'UTR +6bp/+6bp and ERCC1-118C/T or C/C genotypes may better receive capecitabine instead of 5FU in an oxaliplatin-based first-line treatment.
European Journal of Cancer 07/2008; 44(9):1229-37. DOI:10.1016/j.ejca.2008.03.025 · 5.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The incidence and prevalence of comorbid conditions in lung cancer patients increase with age. The aim of the study was to determine response and tolerability with the biweekly combination gemcitabine-vinorelbine in elderly non-small-cell lung cancer (NSCLC) patients. In order to characterise the population included in the study well and assess the results achieved properly, an evaluation of the functional status, comorbidity and survival was performed.
Between June 2001, and December 2003, 59 untreated advanced NSCLC patients over the age of 70 years entered the study. Treatment consisted of gemcitabine 1750 mg/m(2) and vinorelbine 30 mg/m(2) on day 1 every two weeks. The response was evaluated every f ive cycles (RECIST guidelines). Comorbidity was evaluated according to the Charlson and Kaplan Feinstein scales. To measure functional status, activities of daily living (ADL) and instrumental ADL (IADL) were considered.
Median age was 74; ECOG performance status was >2 in 59.3%; no dependence in ADL or IADL was found in 24.8% and 42.4% of patients, respectively. A total of 381 courses were administered. Grade 3-4 neutropenia was present in 6.8% of these courses and correlated with IADL. Objective response was 22% (95% CI 12-32). Mean global survival and cause-specific survival were 29 weeks (95% CI 19.9-38.1) and 32 weeks (95% CI 23.4-40.8) respectively. Comorbidity displayed no close correlation with functional status, but comorbidity according to the Kaplan Feinstein index correlated with IADL. Performance status, ADL, IADL and weight loss were significantly related to survival in multivariate analysis.
This biweekly combination is feasible in elderly lung cancer patients with a high burden of comorbidity and dependence. Toxicity is acceptable, whereas response rate and survival fall in the range of active regimens. ADL and IADL indices allow the identification of elderly patients with a worse prognosis.
[Show abstract][Hide abstract] ABSTRACT: Docetaxel is a widely accepted second-line treatment in advanced non-small-cell lung cancer (NSCLC) with a risk of myelotoxicity. This study evaluated the efficacy and toxicity profile of two docetaxel regimens in NSCLC patients who had failed first-line non-docetaxel-based chemotherapy.
A total of 259 patients from 33 Spanish centers were randomized to receive either docetaxel 75 mg/m(2) administered every 3 weeks (3W arm) or docetaxel 36 mg/m(2) given weekly (1W arm) for 6 weeks followed by 2 weeks of rest. The primary end point was 1-year survival; secondary end points were median survival, time to progression, response and toxicity.
One-year survival was 27% in the 3W and 22% in the 1W arm. Median time to progression was also similar in the two arms. Median survival was 6.6 months in the 3W arm versus 5.4 months in the 1W arm (P = 0.075). Response rates were 9.3% in the 3W arm and 4.8% in the 1W arm. More patients in the 1W arm experienced mucositis [1W, nine patients (7.2%); 3W, two patients (1.6%); P = 0.032], while febrile neutropenia was significantly higher in the 3W arm [3W, 10 patients (7.8%); 1W, one patient (0.8%); P = 0.010].
Both weekly and 3-weekly docetaxel were effective and well-tolerated, with different toxicity profiles. In general, there was no indication to recommend the weekly schedule. However, the significant lower rate of febrile neutropenia observed in the weekly schedule makes it a good alternative for patients at risk of severe neutropenia.
Annals of Oncology 04/2006; 17(3):467-72. DOI:10.1093/annonc/mdj115 · 7.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Elderly patients constitute a subpopulation with special characteristics that differ from those of the nonelderly and have been underrepresented in clinical trials. This study was performed to determine the efficacy and safety of irinotecan (CPT-11) in combination with fluorouracil (FU) administered as a 48-hour continuous infusion twice a month in elderly patients.
Patients > or = 72 years old with metastatic colorectal cancer, Eastern Cooperative Oncology Group performance status of 0 to 1, no geriatric syndromes, and no prior treatment were treated every 2 weeks with CPT-11 180 mg/m2 plus FU 3,000 mg/m2 in a 48-hour continuous infusion.
By intent-to-treat analysis, in 85 assessable patients, the objective response rate was 35% (95% CI, 25% to 46%), and stable disease was 33% (95% CI, 23% to 44%). Median time to progression was 8.0 months (95% CI, 6.0 to 10.0 months), and median overall survival time was 15.3 months (95% CI, 13.8 to 16.9 months). Toxicity was moderate. Grade 3 and 4 neutropenia, diarrhea, and asthenia were observed in 21%, 17%, and 13% of patients, respectively. Only one case of neutropenic fever occurred. There were two toxic deaths, one was a result of grade 4 diarrhea and acute kidney failure, and the other was a result of massive intestinal hemorrhage in the first cycle. The study of prognostic factors did not reveal any predictive factor of response. Response to treatment and baseline lactate dehydrogenase were the main factors conditioning progression-free and overall survival.
Twice a month continuous-infusion CPT-11 combined with FU is a valid therapeutic alternative for elderly patients in good general condition.
[Show abstract][Hide abstract] ABSTRACT: The combination of irinotecan and raltitrexed is safe and active in 5-fluorouracil-refractory, metastatic colorectal cancer (CRC), with the advantage of its convenient three-weekly schedule. The aim of this multicenter phase II study was to assess its efficacy and toxicity in first-line treatment.
Between May 2000 and March 2001, 62 previously untreated patients received irinotecan (350 mg/m(2)) plus raltitrexed (3 mg/m(2)), with courses repeated every 21 days. Objective response was assessed every three courses, and treatment maintained until tumor progression or unacceptable toxicity.
A total of 331 cycles were administered, with a median of five cycles per patient (range, 1-16). Seventeen patients achieved a partial response and 2 a complete response, for an overall intention-to-treat response rate of 30% (95% confidence interval, 18-44%). The incidence of grade 3-4 toxicity per patient was diarrhea (27%), emesis (13%), anemia (12%), neutropenia (9%), and asthenia (7%). Three patients (5%) died from treatment-related adverse events (diarrhea plus neutropenia). The median potential follow-up is now 37 months. Median survival was 12.2 months, and median time to progression was 6.3 months.
The combination of irinotecan plus raltitrexed is an easy comfortable schedule for patients with metastatic CRC, but both efficacy and toxicity results seem suboptimal for first-line treatment.