Concurrent palliative chemoradiation leads to survival and quality of life benefits in poor prognosis stage III non-small-cell lung cancer: a randomised trial by the Norwegian Lung Cancer Study Group

Background: The palliative role of chemoradiation in the treatment of patients with locally advanced, inoperable non-small-cell lung cancer stage III and negative prognostic factors remains unresolved. Methods: Patients not eligible for curative radiotherapy were randomised to receive either chemoradiation or chemotherapy alone. Four courses of intravenous carboplatin on day 1 and oral vinorelbin on days 1 and 8 were given with 3-week intervals. Patients in the chemoradiation arm also received radiotherapy with fractionation 42 Gy/15, starting at the second chemotherapy course. The primary end point was overall survival; secondary end points were health-related quality of life (HRQOL) and toxicity. Results: Enrolment was terminated due to slow accrual after 191 patients from 25 Norwegian hospitals were randomised. Median age was 67 years and 21% had PS 2. In the chemotherapy versus the chemoradiation arm, the median overall survival was 9.7 and 12.6 months, respectively (Po0.01). One-year survival was 34.0% and 53.2% (Po0.01). Following a minor decline during treatment, HRQOL remained unchanged in the chemoradiation arm. The patients in the chemotherapy arm reported gradual deterioration during the subsequent months. In the chemoradiation arm, there were more hospital admissions related to side effects (Po0.05). Conclusion: Chemoradiation was superior to chemotherapy alone with respect to survival and HRQoL at the expense of more hospital admissions due to toxicity

“The challenge is the complexity” – A qualitative study about decision-making in advanced lung cancer treatment

Introduction The value of shared decision-making and decision aids (DA) has been well documented yet remain difficult to integrate into clinical practice. We wanted to investigate needs and challenges regarding decision-making about advanced lung cancer treatment after first-line therapy, focusing on DA applicability. Methods Qualitative data from separate, semi-structured focus groups with patients/relatives and healthcare professionals were analysed using systematic text condensation. 12 patients with incurable lung cancer, seven relatives, 12 nurses and 18 doctors were recruited from four different hospitals in Norway. Results The participants described the following needs and challenges affecting treatment decisions: 1) Continuity of clinician-patient-relationships as a basic framework for decision-making; 2) barriers to information exchange; 3) negotiation of autonomy; and 4) assessment of uncertainty and how to deal with it. Some clinicians feared DA would steal valuable time and disrupt consultations, arguing that such tools could not incorporate the complexity and uncertainty of decision-making. Patients and relatives reported a need for more information and the possibility both to decline or continue burdensome therapy. Participants welcomed interventions supporting information exchange, like communicative techniques and organizational changes ensuring continuity and more time for dialogue. Doctors called for tools decreasing uncertainty about treatment tolerance and futile therapy. Conclusion Our study suggests it is difficult to develop an applicable DA for advanced lung cancer after first-line therapy that meets the composite requirements of stakeholders. Comprehensive decision support interventions are needed to address organizational structures, communication training including scientific and existential uncertainty, and assessment of frailty and treatment toxicity.publishedVersio

Simplifying Treatment of Advanced Non-small Cell Lung Cancer : Regimen, Route of Administration, and Patients' Preferences

Lung cancer is the cancer disease that takes the most lives. Non-small cell lung cancer (NSCLC) is the most common type, and more than half have an incurable disease at the time of diagnosis. Chemotherapy can halt the disease but is only moderately effective, has some side effects and requires regular hospital visits for intravenous infusions. The aim of the current work was to find a more tolerable treatment that is easier to administer and to explore how patients balance the benefits and disadvantages of treatment. We conducted a national study comparing a chemotherapy combination with fewer side effects (vinorelbine and gemcitabine; VG) with the most commonly used combination in Norway (vinorelbine and carboplatin; VC). Both regimens had a 3-week cycle, with carboplatin given on day 8 and the other drugs on days 1 and 8. The patients went through three cycles. We used vinorelbine in capsule form (oral vinorelbine). This allowed comparison with previous studies in Norway that used intravenous vinorelbine. We also interviewed patients about how large the treatment effect should be to accept treatment. The VG combination was no better than VC, in terms of overall survival and health related quality of life (HRQoL), and VC remained the preferred regimen for most patients. Oral vinorelbine had a favourable toxicity profile without compromising survival outcomes. Oral vinorelbine have replaced intravenous vinorelbine on day 8, which allow for home treatment and simplifying the treatment. Studying patients’ attitudes to treatment at the time of diagnosis was complicated. This study suggested that most patients accepted the planned treatment even if the benefits were minimal

Associations between hematologic toxicity and health-related quality of life during first-line chemotherapy in advanced non-small-cell lung cancer: a pooled analysis of two randomized trials

Background: Many patients experience toxicity from chemotherapy that may negatively impact their health-related quality of life (HRQoL), but side effects often go undetected by health care personnel. Our aim was to investigate whether hematologic toxicity (HT) was associated with HRQoL impairment, and, consequently, if blood counts could be used to identify patients with the highest need for supportive care during chemotherapy. Material and methods: Data from two phase III trials of first-line chemotherapy in advanced non-small-cell lung cancer (NSCLC) were analyzed (n = 873). Blood counts were measured weekly in the treatment period. We categorized patients as having severe (CTCAE grade 3–4) or non-severe (grade 0–2) HT during the first chemotherapy cycle. HRQoL was reported on the EORTC QLQ-C30 and LC13 before and at the end of the cycle. The primary endpoints were changes in global quality of life, fatigue, nausea/vomiting and dyspnea (LC13). Results: Of the 766 patients with complete data set, 177 (23%) developed severe HT during the first chemotherapy cycle. Changes in fatigue and nausea/vomiting were significantly worse for patients experiencing severe compared to patients with non-severe HT (difference in mean change of 4.9 points; p = .01, and 6.4 points; p = .01, respectively), but this association was limited to neutropenia, not thrombocytopenia or anemia. There were no significant associations between HT and global quality of life or dyspnea (difference in mean change of 2.1 points; p = .28, and 3.3 points; p = .053, respectively). Conclusions: Patients developing severe HT had worse changes in two out of four of the primary HRQoL endpoints, but the association was not strong enough to use blood counts to identify patients who need more clinical attention and supportive care during chemotherapy

Tumour size reduction after the first chemotherapy-course and outcomes of chemoradiotherapy in limited disease small-cell lung cancer

Objectives: Concurrent chemotherapy and thoracic radiotherapy (TRT) is recommended for limited disease small-cell lung cancer (LD SCLC). TRT should start as early as possible, often meaning with the second course due to patient referral time and the fact that TRT planning takes time. Early assessment of response to the first course of chemotherapy may be a useful way to individualise treatment. The aims of this study were to assess tumour size reduction after the first chemotherapy-course, and whether this reduction was associated with outcomes in LD SCLC. Material and methods: A randomised trial comparing twice-daily (45 Gy/30 fractions) with once-daily (42 Gy/15 fractions) TRT, given concurrently with four courses of cisplatin/etoposide (n = 157) was the basis for this study. Tumour size was assessed on CT scans at baseline and planning scans for TRT according to RECIST 1.0. Results: CT scans were available for 135 patients (86%). Ninety-four percent had a reduction in tumour size after the first chemotherapy-course. The median reduction in sum of diameters (SOD) of measurable lesions was ÷16 mm (÷84 to +10 mm), corresponding to ÷18% (÷51 to +12%). Eighty-two percent had stable disease, 18% partial response. Reduction in SOD was significantly associated with complete response at first follow-up (OR: 1.05, 95% CI 1.01–1.09; p=0.013), PFS (HR: 0.97, 95% CI 0.96-0.99; p=0.001), and overall survival (HR: 0.98, 95% CI 0.96–1.00; p=0.010). Conclusion: Response from the first course of chemotherapy had a significant positive association with outcomes from chemoradiotherapy, and might be used to stratify and randomise patients in future studies

Comorbidity and outcomes of concurrent chemo- and radiotherapy in limited disease small cell lung cancer

Background: Many patients with limited disease small cell lung cancer (LD SCLC) suffer from comorbidity. Not all patients with comorbidity are offered standard treatment, though there is little evidence for such a policy. The aim of this study was to investigate whether patients with comorbidity had inferior outcomes in a LD SCLC cohort. Material and methods: We analyzed patients from a randomized study comparing two three-week schedules of thoracic radiotherapy (TRT) plus standard chemotherapy in LD SCLC. Patients were to receive four courses of cisplatin/etoposide and TRT of 45 Gy/30 fractions (twice daily) or 42 Gy/15 fractions (once daily). Responders received prophylactic cranial irradiation (PCI). Comorbidity was assessed using the Charlson Comorbidity Index (CCI), which rates conditions with increased one-year mortality. Results: In total 157 patients were enrolled between May 2005 and January 2011. Median age was 63 years, 52% were men, 16% had performance status 2, and 72% stage III disease. Forty percent had no comorbidity; 34% had CCI-score 1; 15% CCI 2; and 11% CCI 3–5. There were no significant differences in completion rates of chemotherapy, TRT or PCI across CCI-scores; or any significant differences in the frequency of grade 3–5 toxicity (p = 0.49), treatment-related deaths (p = 0.36), response rates (p = 0.20), progression-free survival (p = 0.18) or overall survival (p = 0.09) between the CCI categories. Conclusion: Patients with comorbidity completed and tolerated chemo-radiotherapy as well as other patients. There were no significant differences in response rates, progression-free survival or overall survival – suggesting that comorbidity alone is not a reason to withhold standard therapy in LD SCLC

Vinorelbine and gemcitabine vs vinorelbine and carboplatin as first-line treatment of advanced NSCLC. A phase III randomised controlled trial by the Norwegian Lung Cancer Study Group

Background: Platinum-based doublet chemotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC), but earlier studies have suggested that non-platinum combinations are equally effective and better tolerated. We conducted a national, randomised study to compare a non-platinum with a platinum combination. Methods: Eligible patients had stage IIIB/IV NSCLC and performance status (PS) 0–2. Patients received up to three cycles of vinorelbine 60 mg m−2 p.o.+gemcitabine 1000 mg m−2 i.v. day 1 and 8 (VG) or vinorelbine 60 mg m−2 p.o. day 1 and 8+carboplatin area under the curve=5 (Calvert's formula) i.v. day 1 (VC). Patients ⩾75 years received 75% of the dose. Endpoints were overall survival, health-related quality of life (HRQoL), toxicity, and the use of radiotherapy. Results: We randomised 444 patients from September 2007 to April 2009. The median age was 65 years, 58% were men and 25% had PS 2. Median survival was VG: 6.3 months; VC: 7.0 months, P=0.802. Vinorelbine plus carboplatin patients had more grade III/IV nausea/vomiting (VG: 4%, VC: 12%, P=0.008) and grade IV neutropenia (VG: 7%, VC: 19%, P<0.001). Infections, HRQoL and the use of radiotherapy did not differ significantly between the treatment groups. Conclusion: The two regimens yielded similar overall survival. The VG combination had only a slightly better toxicity profile

Vinorelbine and gemcitabine vs vinorelbine and carboplatin as first-line treatment of advanced NSCLC. A phase III randomised controlled trial by the Norwegian Lung Cancer Study Group

BACKGROUND: Platinum-based doublet chemotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC), but earlier studies have suggested that non-platinum combinations are equally effective and better tolerated. We conducted a national, randomised study to compare a non-platinum with a platinum combination. METHODS: Eligible patients had stage IIIB/IV NSCLC and performance status (PS) 0-2. Patients received up to three cycles of vinorelbine 60 mg m -2 p.o. þ gemcitabine 1000 mg m -2 i.v. day 1 and 8 (VG) or vinorelbine 60 mg m-2 p.o. day 1 and 8 þ carboplatin area under the curve ¼ 5 (Calvert’s formula) i.v. day 1 (VC). Patients X75 years received 75% of the dose. Endpoints were overall survival, health-related quality of life (HRQoL), toxicity, and the use of radiotherapy. RESULTS: We randomised 444 patients from September 2007 to April 2009. The median age was 65 years, 58% were men and 25% had PS 2. Median survival was VG: 6.3 months; VC: 7.0 months, P ¼ 0.802. Vinorelbine plus carboplatin patients had more grade III/IV nausea/vomiting (VG: 4%, VC: 12%, P ¼ 0.008) and grade IV neutropenia (VG: 7%, VC: 19%, Po0.001). Infections, HRQoL and the use of radiotherapy did not differ significantly between the treatment groups. CONCLUSION: The two regimens yielded similar overall survival. The VG combination had only a slightly better toxicity profile

Comorbidity and outcomes of concurrent chemo- and radiotherapy in limited disease small cell lung cancer

Background: Many patients with limited disease small cell lung cancer (LD SCLC) suffer from comorbidity. Not all patients with comorbidity are offered standard treatment, though there is little evidence for such a policy. The aim of this study was to investigate whether patients with comorbidity had inferior outcomes in a LD SCLC cohort. Material and methods: We analyzed patients from a randomized study comparing two three-week schedules of thoracic radiotherapy (TRT) plus standard chemotherapy in LD SCLC. Patients were to receive four courses of cisplatin/etoposide and TRT of 45 Gy/30 fractions (twice daily) or 42 Gy/15 fractions (once daily). Responders received prophylactic cranial irradiation (PCI). Comorbidity was assessed using the Charlson Comorbidity Index (CCI), which rates conditions with increased one-year mortality. Results: In total 157 patients were enrolled between May 2005 and January 2011. Median age was 63 years, 52% were men, 16% had performance status 2, and 72% stage III disease. Forty percent had no comorbidity; 34% had CCI-score 1; 15% CCI 2; and 11% CCI 3–5. There were no significant differences in completion rates of chemotherapy, TRT or PCI across CCI-scores; or any significant differences in the frequency of grade 3–5 toxicity (p ¼ 0.49), treatment-related deaths (p ¼ 0.36), response rates (p ¼ 0.20), progression-free survival (p ¼ 0.18) or overall survival (p ¼ 0.09) between the CCI categories. Conclusion: Patients with comorbidity completed and tolerated chemo-radiotherapy as well as other patients. There were no significant differences in response rates, progression-free survival or overall survival – suggesting that comorbidity alone is not a reason to withhold standard therapy in LD SCLC