Does postoperative chemotherapy have a survival benefit for patients with pancreatic cancer?

In our study, we investigated whether postoperative chemotherapy improved survival in patients with invasive ductal carcinoma of the pancreas. Between 1987 and 2004, 111 patients underwent pancreatic resection against invasive ductal carcinoma of the pancreas in Wakayama Medical University Hospital. Median survival time (MST) was 19.4 months, 8.6 months, and 7.2 months, in JPS Stage III (UICC Stage IIA and IIB), JPS Stage IVa (UICC Stage IIA and IIB), and JPS Stage IVb (UICC Stage IV), respectively (P < 0.01). The MST of the chemotherapy group was 12 months, and the MST of the non-chemotherapy group was 8.4 months (P < 0.05). Moreover, in JPS Stage IV (UICC Stage IIA, IIB, III, and IV) highly advanced pancreatic cancer, the MST of the chemotherapy group was 10.9 months, and the MST of the group without chemotherapy was 6.6 months (P < 0.01). Since pancreatic cancer is characterized by an aggressive tumor with a high recurrent rate, postoperative chemotherapy is effective for an improvement of survival.     

Do all patients with advanced non-small-cell lung cancer benefitfrom cisplatin-based combination therapy?

Background:Platinum-based chemotherapy has been shown to beeffective in improving survival and quality of life in advancednon-small-cell lung cancer (NSCLC) patients. The objective of this studywas to identify patients more likely to benefit from chemotherapy inorder to avoid the indiscriminate treatment of all patients. Patients and methods:A multivariate analysis of survivalwas performed using the database of the European randomized phase IIItrial that compared vinorelbine (navelbine®) (NVB),vinorelbine–cisplatin (NVB-P) and vindesine–cisplatin(VDS-P) in 612 patients with inoperable NSCLC (stage III or IV).Interactions between treatment and the prognostic factors singled out bythe Cox procedure were specifically tested. Results:Theperformance status (PS) was the only significant interaction among theselected prognostic factors and treatment. Subgroup analysis showed thatthe advantage obtained with NVB-P predominantly concerned PS 0–1patients, whose median survival lasted 43 weeks (95% confidenceinterval (95% CI): 39–50 weeks) with a one-year survivalrate of 38% (95% CI: 31%–46%)versus36 weeks (95% CI: 30–40 weeks) and34% (95% CI: 27%–42%) for NVB alone,and 33 weeks (95% CI: 30–39 weeks) and 29%(95% CI: 22%–36%) for VDS-P. In sharpcontrast, survival in PS 2 patients was similar (median 18 weeks)(NVB-P 95% CI: 11–34 weeks; NVB 95% CI: 11–35weeks; VDS-P 95% CI: 14–32 weeks) whatever thetreatment. Conclusion:PS 2 patients with advancedNSCLC might not benefit from cisplatin combination therapy.     

Should adjuvant chemotherapy become standard treatment in all patients with resected non-small-cell lung cancer?

Surgery remains the main curative treatment for patients with early-stage non-small-cell lung cancer (NSCLC); however, because many patients probably have undetectable micrometastasis even at diagnosis, adjuvant treatment is usually needed. The results for radiotherapy have mostly been disappointing, and a strong emphasis has, therefore, been placed on chemotherapy as the preferred modality. Adjuvant chemotherapy, and in particular, platinum-based regimens, have been assessed in several studies, but the results have been conflicting. Most trials have included patients with a wide range of disease stages and have shown, at most, only moderate improvements in survival. Thus, although clearly indicated in some patients, whether adjuvant chemotherapy should be used in all patients with resected disease is highly controversial. In this debate, Thierry Le Chevalier and colleagues and Giorgio Scagliotti present opposing arguments for whether this approach should be considered standard.     

Is chemotherapy in elderly patients with metastatic or recurrent gastric cancer as tolerable and effective as in younger patients?

Aim: To analyze the chemotherapy regimens and outcomes of advanced gastric cancer (AGC) patients older than 70 years of age. Methods: Between May 2001 and October 2009, 1135 patients with metastatic or recurrent gastric cancer received palliative chemotherapy. Of these patients 56 (4.9%) were ≥70 years old and were analyzed retrospectively. Results: The median age at the time of first‐line chemotherapy was 73 years (range, 70–85) and the median Charlson comorbidity index was 0 (0–5). In all 17 patients (30%) received surgery with curative or palliative intent; 43 (77%) were treated by doublet or triplet first‐line chemotherapy regimens and 13 patients (23%) received single agent chemotherapy. Median progression‐free survival for first‐line chemotherapy was 3.97 months (95% CI 2.05–5.89) with an overall response rate of 26%. After the first‐line chemotherapy, only 18 of 56 (32%) patients received second‐line chemotherapy. The median overall survival (OS) was 12.4 months (95% CI 2.81–21.99). In multivariate analysis, receiving surgery and disease control for first‐line chemotherapy were independent prognostic factors for increased OS for all 56 patients. Conclusion: Patients older ≥70 years with metastatic or recurrent gastric cancer might achieve clinical benefit from chemotherapy. Receiving surgery and response of over more stable disease for first‐line chemotherapy were independent prognostic factors for increased OS.     

Capecitabine “metronomic” chemotherapy for palliative treatment of elderly patients with advanced gastric cancer after fluoropyrimidine-based chemotherapy

We aimed to study the efficacy and safety of metronomic capecitabine in pretreated elderly patients with advanced gastric cancer. Eligible patients with advanced gastric cancer were treated with capecitabine at a fixed dose 1,000 mg daily (days 1–28 continuously, every 5 weeks) until disease progression or significant toxicity. Tumor response was assessed every 10 weeks by computed tomography scan using Response Evaluation Criteria in solid tumors. In total, 45 patients were enrolled, of whom 43 were evaluated for efficacy and 45 for safety. A median of 3 cycles (range 1–12) were administered. Metronomic chemotherapy had a disease control rate (DCR) at 8 weeks of 51.1% (95% CI 25.7–67.8), and the objective response rate was 20.9% (95% CI 13.1–38.5, 9 of 43 assessable patients). The median time-to-progression and median overall survival were 3.6 months (95% CI: 3.2–4.0 months) and 7.6 months (95% CI 7.0–8.2 months), respectively. Grade II neutropenia and thrombocytopenia were observed in 13.3 and 2.2% of patients, respectively. Grade II/III nonhematological toxicities included diarrhea (4.4%), stomatitis (13.4%), and hand–foot syndrome (15.5%). No grade IV toxicity, neutropenic fever or treatment-related deaths occurred. Metronomic capecitabine was effective and well tolerated as palliative treatment in elderly patients with advanced gastric cancer after fluoropyrimidine-based chemotherapy.     

The elderly with synchronous non-small cell lung cancer and solitary brain metastasis: does palliative thoracic radiotherapy have a useful role?

We evaluated the prognosis associated with advanced age by comparing the clinical features of individuals 65 years of age and older to those of younger patients with single metastasis to the brain alone (SMBA) and simultaneous non-small cell lung cancer (NSCLC), and the potential role of palliative thoracic radiotherapy in this cohort of patients. Our 23-year experience included 72 consecutive (22 elderly and 50 non-elderly) people. Older patients predominantly presented with N0-N1 stage disease and coexisting illness. Univariate analysis showed that younger age (p=0.04) and operative removal of SMBA (p=0.01) were predictive of better survival. However, with multivariate analysis, resection of SMBA remained the sole predictor of prognosis. The application of NSCLC radiotherapy for palliation did not favorably alter outcome. In conclusion, elderly patients with simultaneous NSCLC and SMBA seem to fare less well than their younger counterparts. Moreover, the concurrent application of radiotherapy for palliation of the lung neoplasm was not prognostically advantageous.     

Do elderly people with lung cancer benefit from palliative radiotherapy?

The median age at diagnosis of patients with lung cancer is currently around 70 and is rising, yet the trials on which treatment is based included few elderly people. We conducted a prospective observational cohort study of 83 elderly patients (aged 75 and above) being treated with palliative radiotherapy for lung cancer, with a comparison group of 49 younger patients (aged 65 and under). Response to treatment was evaluated by patient-assessed symptom and quality of life scores using the EORTC QLQ-C30 and its companion lung module LC17. This is to date the largest prospective study of elderly lung cancer patients in routine practice. We found no significant differences in response or toxicity between the two groups. Elderly people with lung cancer should be offered palliative radiotherapy the same as younger patients, with the same expectation of benefit.     

Safety and efficacy of weekly nab®-paclitaxel in combination with carboplatin as first-line therapy in elderly patients with advanced non-small-cell lung cancer

BackgroundThis analysis evaluates safety and efficacy in elderly (≥70 years old) versus younger patients enrolled in a phase III advanced non-small-cell lung cancer (NSCLC) trial.Patients and MethodsUntreated stage IIIB/IV patients with PS 0/1 were randomly assigned (1:1) to carboplatin AUC6, day 1 every 3 weeks, and either nab-paclitaxel (Abraxane) 100 mg/m² weekly (nab-P/C) or solvent-based paclitaxel (Taxol) 200 mg/m² day 1 every 3 weeks (sb-P/C). The primary end-point was overall response rate (ORR).ResultsFifteen percent of 1052 enrolled patients were elderly: nab-P/C, n = 74; sb-P/C, n = 82. In both age cohorts, the ORR was higher with nab-P/C versus sb-P/C (age ≥70: 34% versus 24%, P = 0.196; age <70: 32% versus 25%, P = 0.013). In elderly patients, progression-free survival (PFS) trended in favor of nab-P/C (median 8.0 versus 6.8 months, hazard ratio (HR) 0.687, P = 0.134), and overall survival (OS) was significantly improved (median 19.9 versus 10.4 months, HR 0.583, P = 0.009). In younger patients, PFS (median 6.0 versus 5.8 months, HR 0.903, P = 0.256) and OS (median 11.4 versus 11.3 months, HR 0.999, P = 0.988) were similar in both arms. Adverse events were similar in both age groups, with less neutropenia (P = 0.015), neuropathy (P = 0.001), and arthralgia (P = 0.029), and increased anemia (P = 0.007) with nab-P/C versus sb-P/C.ConclusionsIn elderly NSCLC patients, nab-P/C as first-line therapy was well tolerated and improved the ORR and PFS, with substantially longer OS versus sb-PC.     

Does c-Met remain a rational target for therapy in patients with EGFR TKI-resistant non-small cell lung cancer?

Non-small cell lung cancer (NSCLC) inevitably develops resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. In 5–20% of cases, this can be attributed to aberrant c-Met activity, providing a clear rationale for the use of c-Met inhibitors in these patients. EGFR TKI-resistant tumors often remain sensitive to EGFR signaling, such that c-Met inhibitors are likely to be most effective when combined with continued EGFR TKI therapy. The phase III trials of the c–Met inhibitors onartuzumab and tivantinib, which failed to demonstrate significant benefit in patients with NSCLC but excluded patients with EGFR TKI-resistant disease, do not allow c-Met to be dismissed as a rational target in EGFR TKI-resistant NSCLC. Selective c-Met TKIs exhibit more favorable properties, targeting both hepatocyte growth factor (HGF)-dependent and -independent c-Met activity, with a reduced risk of toxicity compared to non-selective c-Met TKIs. Phase Ib/II trials of the selective c-Met TKIs capmatinib and tepotinib have shown encouraging signs of efficacy. Factors affecting the success of ongoing and future trials of c-Met inhibitors in patients with EGFR TKI-resistant, c-Met-positive NSCLC are considered.     

Do patients with weight loss have a worse outcome when undergoing chemotherapy for lung cancers?

To examine whether weight loss at presentation influences outcome in patients who received chemotherapy for lung cancer or mesothelioma. Multivariate analysis of prospectively collected data 1994-2001. Data were available for age, gender, performance status, histology, stage, response, toxicity, progression-free and overall survival. The outcomes of patients with or without weight loss treated with chemotherapy for small cell lung cancer (SCLC; n=290), stages III and IV non-small-cell lung cancer (NSCLC; n=418), or mesothelioma (n=72) were compared. Weight loss was reported by 59, 58 and 76% of patients with SCLC, NSCLC and mesothelioma, respectively. Patients with weight loss and NSCLC (P=0.003) or mesothelioma (P=0.05) more frequently failed to complete at least three cycles of chemotherapy. Anaemia as a toxicity occurred significantly more frequently in NSCLC patients with weight loss (P=0.0003). The incidence of other toxicities was not significantly affected by weight loss. NSCLC patients with weight loss had fewer symptomatic responses (P=0.001). Mesothelioma patients with weight loss had fewer symptomatic (P=0.03) and objective responses (P=0.05). Weight loss was an independent predictor of shorter overall survival for patients with SCLC (P=0.003, relative risk (RR)=1.5), NSCLC (P=0.009, RR=1.33) and mesothelioma (P=0.03, RR=1.92) and an independent predictor of progression-free survival in patients with SCLC (P=0.01, RR=1.43). In conclusion, weight loss as a symptom of lung cancer predicts for toxicity from treatment and shorter survival.     

Second-line treatment of non-small-cell lung cancer: chemotherapy or tyrosine kinase inhibitors?

After first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC), many patients remain candidates for a second-line treatment. Docetaxel, pemetrexed and erlotinib are currently approved in the USA and Europe as second-line therapy for NSCLC, while gefitinib is approved and licensed in Europe, but not in the USA, for EGF receptor-mutated patients in the same setting. Results of the registration trials for these four agents show similar efficacy in terms of objective response rate and survival, but significantly different toxicity and tolerability. Therefore, at the time of failure of first-line treatment, it is crucial to evaluate different clinical factors that could help choose the second-line treatment of metastatic NSCLC, as performance status and comorbidities; new predictive biomarkers will be validated in future trials. Considering the different predictive and prognostic factors, tyrosine kinase inhibitors could be a valid option for second-line treatment of NSCLC.     

Second-line treatment of non-small-cell lung cancer: chemotherapy or tyrosine kinase inhibitors?

After first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC), many patients remain candidates for a second-line treatment. Docetaxel, pemetrexed and erlotinib are currently approved in the USA and Europe as second-line therapy for NSCLC, while gefitinib is approved and licensed in Europe, but not in the USA, for EGF receptor-mutated patients in the same setting. Results of the registration trials for these four agents show similar efficacy in terms of objective response rate and survival, but significantly different toxicity and tolerability. Therefore, at the time of failure of first-line treatment, it is crucial to evaluate different clinical factors that could help choose the second-line treatment of metastatic NSCLC, as performance status and comorbidities; new predictive biomarkers will be validated in future trials. Considering the different predictive and prognostic factors, tyrosine kinase inhibitors could be a valid option for second-line treatment of NSCLC.     

Adjuvant chemotherapy for elderly patients with stage I non-small-cell lung cancer ≥4 cm in size: an SEER–Medicare analysis

We have used population-based data from the SEER–Medicare registry to show that adjuvant chemotherapy is associated with improved survival among elderly patients with early-stage non-small-cell lung cancer ≥4 cm. These findings extend the results of a prior RCT to the growing population of older patients with cancer.BackgroundThe role of adjuvant chemotherapy for non-small-cell lung cancer (NSCLC) stage I patients with tumors size ≥4 cm is not well established in the elderly.Patients and methodsWe identified 3289 patients with stage I NSCLC (T2N0M0 and tumor size ≥4 cm) who underwent lobectomy from the Surveillance, Epidemiology and End Results (SEER)–Medicare linked database diagnosed from 1992 to 2009. Overall survival and rates of serious adverse events (defined as those requiring admission to hospital) were compared between patients treated with resection alone, platinum-based adjuvant chemotherapy, or postoperative radiation (PORT) with or without adjuvant chemotherapy. Propensity scores for receiving each treatment were calculated and survival analyses were conducted using inverse probability weights based on the propensity score.ResultsOverall, 84% patients were treated with resection alone, 9% received platinum-based adjuvant chemotherapy, and 7% underwent PORT with or without adjuvant chemotherapy. Adjusted analysis showed that adjuvant chemotherapy [hazard ratio (HR), 0.82; 95% confidence interval (CI) 0.68–0.98] was associated with improved survival compared with resection alone. Conversely, the use of PORT with or without adjuvant chemotherapy (HR 1.91; 95% CI 1.64–2.23) was associated with worse outcomes. Patients receiving adjuvant chemotherapy had more serious adverse events compared with those treated with resection alone, with neutropenia (odds ratio, 21.2; 95% CI 5.8–76.6) being most significant. No significant difference was observed in rates of fever, cytopenias, nausea, and renal dysfunction.ConclusionsPlatinum-based adjuvant chemotherapy is associated with reduced mortality and increased serious adverse events in elderly patients with stage I NSCLC and tumor size ≥4 cm.