Prevalence of emotional distress in newly diagnosed lung cancer patients.

GOALS OF WORK: Distress is defined by the National Comprehensive Cancer Network as a multifactorial unpleasant emotional experience of a psychological, social, and/or spiritual nature that may interfere with the ability to cope effectively with cancer. We investigated the prevalence and associated symptoms of distress in newly diagnosed lung cancer patients. PATIENTS AND METHODS: Between November 2005 and July 2007, 98 newly diagnosed lung cancer patients completed an assessment. The Distress Thermometer (DT) and Edmonton Symptom Assessment Scale (ESAS) were used as screening tools. MAIN RESULTS: Fifty (51%) patients reported clinically significant distress (>or=4) on the DT. Of those, 26 (52%) patients reported high levels of depression, nervousness, or both on ESAS. The remaining 24 (48%) patients had elevated levels of distress but no significant depression or nervousness. A correlation between the DT and the total ESAS score was observed (Pearson correlation = 0.46). The ten items of the ESAS together explained 46% of the variability in DT scores. The depression and nervousness ESAS items were significant predictors of DT score (p < 0.01 for both items). However, once the two psychosocial items, depression and nervousness, were removed from the total ESAS score, leaving only physical symptoms and the sleeplessness item, the predictive power of the model decreased to R(2) = 0.12. CONCLUSIONS: The prevalence of distress in lung cancer patients is high. The DT appears to discriminate between physical and emotional distress. This easily measured score may determine which patients require further intervention for emotional distress.

Prognostic value of the six-minute walk in advanced non-small cell lung cancer.

BACKGROUND: The 6 minute walk (6MW) is usually used to evaluate exercise capacity in a variety of patient populations. We hypothesized that the 6MW would decline after chemotherapy and assessed the prognostic value of this test. MATERIALS AND METHODS: The 6MW was conducted in newly diagnosed advanced non-small cell lung cancer patients on three different days: twice before (one initial and one prechemotherapy test) and once after two cycles of chemotherapy. RESULTS: Sixty-four patients were enrolled and 45 (70%) completed the study. For patients who dropped out the distance on initial 6MW was 361 m (SD 99) compared with 445 m (SD 85) for completers (p = 0.004).In the 45 completers, the mean 6MW decreased significantly after two cycles. There was a clinically significant (>54 m) decline in 6MW in 13 patients (29%), and an improved/unchanged 6MW in 32 patients (71%).For patients who walked <400 m on initial 6MW, rates of drop out were significantly higher (p = 0.02), progression of disease was statistically more frequent (p = 0.03), and median survival was significantly shorter: 6.7 months (95% confidence interval 2.6-10.8) compared with 13.9 months (95% confidence interval 10.0-17.8) in patients walking > or =400 m (p = 0.01).An initial 6MW of > or =400 m was the only variable with a significant effect on survival in a Cox regression after adjusting for all known covariates of interest. CONCLUSIONS: The 6MW declines significantly after two cycles of chemotherapy. This decline may have been even greater as patients with lower 6MW were more likely to drop out of the study. An initial 6MW > or =400 m might be a useful prognostic factor for survival in patients with advanced non-small cell lung cancer.

Should patient-rated performance status affect treatment decisions in advanced lung cancer?

INTRODUCTION: The Eastern Cooperative Oncology Group (ECOG) score is a well known prognostic factor and almost always used to determine eligibility for clinical trials. The patient-rated performance status score (Pt-PS), section of the patient generated subjective global assessment scale, has identical criteria to the physician-rated ECOG scale (MD-PS). We compared the Pt-PS with MD-PS in patients with advanced non-small cell lung cancer and compared the effect of each rating on eligibility for a hypothetical clinical trial. METHODS: Consecutive patients with newly diagnosed advanced non-small cell lung cancer completed a patient generated subjective global assessment self-rated questionnaire, which was then correlated (kappa statistic) with the ECOG PS recorded at the same time. Patients were treated with standard chemotherapy. Survival was determined using Kaplan-Meier statistics. RESULTS: One hundred nine patients (M:F-54:55) were recruited. Pt-PS differed from MD-PS in 59 (54%) instances (p = 0.0001). When scores were not congruent, 41/59 (69%) patients evaluated themselves as having a worse PS than the physician's rating. Pt-PS was 0 to 1 in 60 (55%) patients whereas MD-PS was 0 to 1 in 78 (72%) patients. The functional status irrespective of evaluator was predictive of survival (p = 0.001 for MD-PS and p = 0.001 for Pt-PS). However, the median survival in those with MD-PS >/=2 was 3.3 (CI; 1.7-4.9) months whereas individuals with Pt-PS >/=2 had a median survival of 6.2 (CI; 5.4-6.9) months. CONCLUSIONS: Pt-PS and MD-PS were not congruent in over half of the cases, with Pt-PS scores usually poorer. Almost half the patients would have excluded themselves from a hypothetical clinical trial (Pt-PS >/=2). This requires prospective evaluation.

Randomized phase II study of gemcitabine plus cisplatin or carboplatin [corrected], with or without cetuximab, as first-line therapy for patients with advanced or metastatic non small-cell lung cancer.

PURPOSE: To evaluate the efficacy of cetuximab added to first-line gemcitabine/platinum in chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: In this noncomparative, randomized trial, chemotherapy-naïve patients with recurrent/metastatic NSCLC (stage IV or stage IIIB with malignant pleural effusion) were eligible. Patients received cisplatin (75 mg/m2 i.v., every 3 weeks) or carboplatin (area under the concentration-versus-time curve of 5 intravenously [i.v.], every 3 weeks), and gemcitabine (1,250 or 1,000 mg/m2 i.v., days 1 and 8) plus cetuximab (400 mg/m2 i.v. day 1, followed by 250 mg/m2 weekly), in arm A, or chemotherapy alone, in arm B. Response rate was the primary end point; safety, progression-free survival, and overall survival were secondary end points. RESULTS: Sixty-five patients were randomly assigned to arm A and 66 to arm B. Partial responses were observed in 18 patients (27.7%; 95% CI, 17.3 to 40.2) in arm A and 12 (18.2%; 95% CI, 9.8 to 29.6) in arm B. Median progression-free survival was 5.09 months for arm A (95% CI, 4.17 to 5.98) and 4.21 months (95% CI, 3.81 to 5.49) in arm B. Median overall survival was 11.99 months (95% CI, 8.80 to 15.18) and 9.26 months (95% CI, 7.43 to 11.79) in arms A and B, respectively. Overall toxicity was acceptable and consistent with the profiles of the individual agents. CONCLUSION: First-line treatment with cetuximab plus gemcitabine/platinum is well tolerated and can be administered safely in patients with advanced NSCLC. Differences in response rate, progression-free survival, and overall survival suggest that the addition of cetuximab to platinum/gemcitabine may improve clinical outcomes. Larger studies are in progress to address this hypothesis.

Evaluation of denaturing high-performance liquid chromatography as a rapid detection method for identification of epidermal growth factor receptor mutations in nonsmall-cell lung cancer.

BACKGROUND: Somatic mutations of the epidermal growth factor receptor (EGFR) gene in nonsmall-cell lung cancer (NSCLC) may predict responsiveness to tyrosine kinase inhibitors. These mutations are commonly identified using DNA sequencing methods. Although considered the gold standard, this approach is time-consuming. In addition, this approach requires large diagnostic specimens and a high ratio of tumor-to-normal-tissue DNA for optimal results. The use of denaturing high-performance liquid chromatography (dHPLC) as a method to screen for the 2 predominant EGFR mutations is reported. METHODS: Clinical specimens from 104 NSCLC patients were analyzed for EGFR mutations in exons 19 and 21. After DNA extraction and polymerase chain reaction (PCR), both direct sequencing and dHPLC were performed and the results were compared. RESULTS: Sequencing revealed a total of 7 mutations: 3 deletion mutations in exon 19 and 4 missense mutations in exon 21. dHPLC showed the presence of genomic alterations in 23 samples, including the 7 identified by sequencing plus 16 additional samples (10 in exon 19 and 1 in exon 21). dHPLC fractions were isolated, reamplified, and sequenced to confirm the results. In serial dilution studies, dHPLC was able to detect mutations in samples containing as little as 1.6% to 6.25% mutated DNA, whereas direct sequencing required at least 30%. CONCLUSIONS: dHPLC is an efficient and more sensitive method for screening for genomic alterations in exons 19 and 21 of the EGFR gene compared with direct sequence analysis. These data suggest that dHPLC should be implemented as a screening tool for detection of EGFR mutations.

Does granulocyte colony-stimulating factor affect survival in patients with advanced non-small cell lung cancer?

BACKGROUND: Platinum-based chemotherapy is standard treatment for patients with advanced lung cancer. The common side effect of this therapy is myelosuppression, for which different stimulating factors are used. In this article, the effect of granulocyte colony-stimulating factor (G-CSF) administration on the survival of patients with unresectable non-small-cell lung cancer (NSCLC) was evaluated. METHODS: The charts of 127 patients, treated with carboplatin-based chemotherapy, were reviewed for histology, stage, performance status, weight loss, treatment regimen, toxicity, and survival. Eighty patients were stage IIIA/IIIB NSCLC; 47 were stage IIIB (pleural effusion) or stage IV. Eighty-one patients (63%) experienced severe (grades 3 and 4) neutropenia. Forty-two patients received G-CSF, 37 patients for severe neutropenia (14 with febrile neutropenia) and five patients for active infection during chemotherapy. RESULTS: Preliminary analyses, both unadjusted (median survival, 20 months versus 13.8 months; log-rank test, p = 0.02) and adjusted for covariates of interest (Cox regression, hazard ratio = 0.62, p = 0.03) showed a significant effect of the use of G-CSF on survival, even though the groups were balanced with respect to stage, performance status, weight loss, and dose intensity of chemotherapy. Patients with grades 3 and 4 neutropenia (whether they received G-CSF or not) had a better survival outcome compared to those who did not have neutropenia (median survival, 17.6 months versus 11.9 months, log-rank test, p = 0.04). A landmark analysis showed a marginally significant effect of G-CSF on survival (median survival, 18.6 months versus 15.1 months, log-rank test, p = 0.08), even after adjustment for covariates. The Cox regression with the use of G-CSF defined as a binary time-varying covariate also showed similar results (Cox regression, hazard ratio = 0.67, 95% CI: 0.42-1.04, p = 0.07). CONCLUSION: In this study, the time bias due to the delayed administration of G-CSF contributed to the longer survival of patients receiving G-CSF. Prospective studies are required to determine whether G-CSF has any effect on survival in patients with advanced NSCLC.

Phase II multicenter study of induction chemotherapy followed by concurrent efaproxiral (RSR13) and thoracic radiotherapy for patients with locally advanced non-small-cell lung cancer.

PURPOSE: Efaproxiral (RSR13) reduces hemoglobin oxygen-binding affinity, facilitates oxygen release, and increases tissue pO2. We conducted a phase II multicenter study that assessed the efficacy and safety of efaproxiral when administered with thoracic radiation therapy (TRT), following induction chemotherapy, for treatment of locally advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-one patients with locally advanced NSCLC were enrolled at 13 sites. Treatment comprised two cycles of paclitaxel (225 mg/m2) and carboplatin (area under the curve, 6), 3 weeks apart, followed by TRT (64 Gy/32 fractions) with concurrent efaproxiral (50 to 100 mg/kg). Survival results were compared with results of study Radiation Therapy Oncology Group (RTOG) 94-10. RESULTS: Overall response rate was 75% (37 of 49 patients). Complete and partial response rates were 6% (three of 49 patients) and 69% (34 of 49 patients), respectively. Median survival time (MST) was 20.6 months (95% CI, 14.0 to 24.2); overall survival rates at 1- and 2-years were 67% and 37%, respectively. Survival results were compared with the sequential (S-CRT) and concurrent (C-CRT) chemoradiotherapy arms of RTOG 94-10. MSTs for cases matched by stage, Karnofsky performance status, and age were: RT-010, 20.6 months; S-CRT, 15.1 months; and C-CRT, 17.9 months. Grade 3 to 4 toxicities related to efaproxiral that occurred in more than one patient included transient hypoxemia (19%), radiation pneumonitis (11%), and fatigue (4%). CONCLUSION: Addition of efaproxiral to S-CRT represents a promising approach in NSCLC treatment, and a randomized study should be pursued. The low incidence of grade 3 to 4 toxicities suggests that the use of efaproxiral instead of a cytotoxic agent, as a radiation sensitizer, may be advantageous.

Sequential therapy with Vinorelbine followed by Gemcitabine in patients with metastatic non small cell lung cancer (NSCLC), performance status (PS) 2, or elderly with comorbidities--a multicenter phase II trial.

BACKGROUND: High risk patients with metastatic non small cell lung cancer (NSCLC) including patients with performance status (PS) 2 or elderly with comorbidities do poorly on combination chemotherapy regimens. We evaluated a sequential treatment with Vinorelbine followed by Gemcitabine to determine its effect on survival and the toxicity in this patient population. METHODS: Forty-two evaluable patients, median age 75, 21 patients with PS 2 and 21 patients with PS 0 or 1, 37 patients with stage IV and five patients with stage III B NSCLC entered the trial. They received Vinorelbine 30 mg/m2, i.v., on days 1+8 every 3 weeks followed by Gemcitabine 1000 mg/m2, i.v., on days 1+8 every 3 weeks, each for two cycles for stable disease or one cycle after best response. Then stable patients continued until progressive disease on Vinorelbine or Gemcitabine according to the patient's preference. RESULTS: A total of 126 cycles of Vinorelbine were administered to 42 patients, median of three cycles per patient and 74 cycles of Gemcitabine, median of 1.0 cycle per patient. Sixteen patients (38%) achieved PR, 11 patients on Vinorelbine, 5 patients on Gemcitabine; 12 patients (26%) had stable disease, 7 patients on Vinorelbine, 5 patients on Gemcitabine. Of 24 patients with progressive disease on Vinorelbine, 3 patients (12.5%) responded to Gemcitabine. Median time-to-first progression was 3.5 months, median survival was 8 months, 1-year survival was 12 patients (28.5%). No grade 3 or 4 toxicities were reported. CONCLUSION: This sequential treatment offers excellent palliative treatment with minimal toxicity for high-risk patients with metastatic NSCLC.