Abnormalities in lipid metabolism have been frequently observed in cancer and are associated with a poor prognosis. However, a detailed, longitudinal characterization of fatty acid status is lacking. This study aimed to assess plasma phospholipid fatty acids before chemotherapy, immediately after and 1 month following chemotherapy in a group of 50 patients newly diagnosed with lung cancer and explore factors which may contribute to aberrations in fatty acids. Their mean ± SD characteristics: age 64 ± 8.5 years, 75% advanced stage disease, body mass index 27.0 ± 5.4 kg/m², 6 month weight loss -4.6 ± 6.1%. Compared to patients with early stage disease, patients with advanced disease had abnormal fatty acid profiles including significantly lower (P
Adjuvant chemotherapy (ACT) is known to improve survival in patients with early-stage non-small cell lung cancer. Herein, we describe chemotherapy regimens used, dose modifications, survival, and treatment-related toxicity in the general population.
All cases of non-small cell lung cancer diagnosed in Ontario in the period 2004-2006 who underwent surgical resection (n = 3354) were identified using the Ontario Cancer Registry in this population-based retrospective cohort study. We linked electronic records of treatment to the registry to identify all cases treated with ACT (n = 1032) and describe drugs, regimens, and dosages delivered. As a proxy measure of ACT-related toxicity, we evaluated deaths and hospitalizations within 16 weeks of starting ACT. Factors associated with dose modification were evaluated by logistic regression. The Cox proportional hazards model was used to describe associations between patient-, disease-, and treatment-related factors and survival.
ACT regimens were identified for 584 of 1032 ACT cases. Almost all cases included cisplatin- or carboplatin-based regimens (478/584, 82%, and 99/584, 17%, respectively). The most common regimen was a vinroelbine/cisplatin doublet (412/584, 71%); 64% of these cases had a dose reduction or omission. Dose modification was not associated with inferior survival on multivariate analysis. Twelve percent of all ACT cases were admitted to hospital within 16 weeks of starting ACT, and there was a 1.6% death rate potentially attributable to ACT. Survival of all ACT cases was comparable with outcomes reported in clinical trials.
ACT regimens used, toxicity, and survival outcomes in the general population are comparable with those reported in clinical trials. Dose modifications used in clinical practice are not associated with inferior survival.
Randomized trials have confirmed the benefits of adjuvant chemotherapy in improving survival in resected early-stage non-small-cell lung cancer (NSCLC). The extent to which these results have translated into clinical practice is unknown.
To examine the referral pattern of patients with resected lung cancer to adjuvant chemotherapy, and to compare compliance and toxicities with current literature.
A retrospective analysis of all patients who underwent a surgical resection for lung cancer at Laval Hospital (Quebec City, Quebec) from March 2004 to January 2006 was conducted.
A total of 258 patients underwent surgery. Seven patients were excluded because of early postoperative death, and two patients were excluded because of incomplete data. Data from 249 patients were analyzed (94% NSCLC). Fifty per cent were referred to medical oncology for consideration of adjuvant chemotherapy, including 37 of 61 patients with stage II NSCLC. One hundred patients received chemotherapy. No significant difference in age, sex, comorbidities and surgical procedures was observed between those who received chemotherapy and those who did not. Chemotherapy was initiated 47 days (median) after the surgery and consisted mainly of cisplatin-vinorelbine (38%), cisplatin-etoposide (22%) and carboplatin-paclitaxel (20%). Sixty-six per cent of the patients completed all four cycles. Grade 3 or 4 toxicities consisted mainly of fatigue (23%) and cytopenia (40%). No death was registered; 15% had to be hospitalized because of adverse effects.
Although adjuvant chemotherapy is gaining acceptance in clinical practice, more patients should be referred to medical oncology following surgical resection. Compliance and toxicity are similar to or better than those described in published randomized trials.
Notes
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Adjuvant chemotherapy in non-small cell lung cancer (NSCLC) has become a new standard of care. This study examines the uptake patterns for adjuvant chemotherapy outside of clinical trials.
A retrospective study of all patients diagnosed with NSCLC in the year 2005 who underwent curative-intent surgery in Nova Scotia, Canada was conducted. Logistic regression models and discriminant function analyses were employed to identify cofactors associated with referral to medical oncology and/or utilization of adjuvant chemotherapy.
Of 540 patients with NSCLC, 108 underwent curative-intent surgery (67% lobectomy; 15% pneumonectomy; 19% wedge resection) for NSCLC (39% IA; 24% IB; 25% II; 14% III). Referral to medical oncology was observed in 44% (47 of 108) of all patients including 73% (30 of 41) of those with stage II-III. Adjuvant chemotherapy utilization was observed in 62% (29 of 47) of those referred including 73% (22 of 30) of those with stage II-III. Overall, 27% (29 of 108) of all patients received adjuvant chemotherapy, including 54% (22 of 41) of those with stage II-III. Higher uptake was significantly associated with age (younger versus older), stage (II/III versus I), and surgery type (pneumonectomy versus wedge). Weaker associations were observed with other cofactors including surgeon, health center, mean household income, and surgery-medical oncologist consult timeline.
The uptake of adjuvant chemotherapy in patients with resected NSCLC outside of clinical trials is low overall, but is higher among younger patients and those with more advanced stages. These uptake patterns may allow future planning of health resource utilization and/or improvement of chemotherapy utilization rates.
Recent trials have shown significant survival benefit from adjuvant chemotherapy for non-small-cell lung cancer (NSCLC). Whether elderly patients tolerate platinum-based adjuvant chemotherapy and derive the same survival advantage is unknown. This retrospective study evaluated the influence of age on survival, adjuvant chemotherapy delivery, and toxicity in National Cancer Institute of Canada (NCIC) Clinical Trials Group study JBR.10.
Pretreatment characteristics and survival were compared for 327 young ( 65 years) patients. Chemotherapy delivery and toxicity were compared for 213 treated patients (63 elderly, 150 young).
Baseline demographics by age were similar with the exception of histology (adenocarcinoma: 58% young, 43% elderly; squamous: 32% young, 49% elderly; P = .001) and performance status (PS; PS 0: 53% young, 41% elderly; P = .01). Chemotherapy significantly prolonged overall survival for elderly patients (hazard ratio, 0.61; 95% CI, 0.38 to 0.98; P = .04). This benefit is similar to the effect for all patients in JBR.10. Mean dose-intensities of vinorelbine and cisplatin were 13.2 and 18.0 mg/m2/wk in young, respectively, and 9.9 and 14.1 mg/m2/wk in elderly patients (vinorelbine, P = .0004; cisplatin, P = .001), respectively. The elderly received significantly fewer doses of vinorelbine (P = .014) and cisplatin (P = .006). Fewer elderly patients completed treatment and more refused treatment (P = .03). There were no significant differences in toxicities, hospitalization, or treatment-related death by age group. Fifteen (11.9%) of 126 deaths in the young resulted from nonmalignant causes, and 15 (21.1%) of 71 in the elderly (P = .13).
Despite elderly patients' receiving less chemotherapy, adjuvant vinorelbine and cisplatin improves survival in patients older than 65 years with acceptable toxicity. Adjuvant chemotherapy should not be withheld from elderly patients.
Although it is commonly assumed that clinical trials are more costly than standard therapy, there have been no previous studies of the cost of conducting phase II trials in lung cancer. We retrospectively analyzed two National Cancer Institute of Canada phase II trials in previously untreated small cell lung cancer (SCLC) to determine the costs of conducting the trials in a cancer treatment centre. Both studies were clinical trials undertaken as part of the NCIC's Investigational New Drug program: IND 69 and IND 50 evaluated docetaxel (taxotere) and gemcitabine, respectively.
data management costs in a Canadian cancer treatment centre were determined from the time estimates provided by data managers to complete various protocol related tasks. Nursing and pharmacy personnel measured the time and supplies necessary to prepare and administer the chemotherapy. Physician fees were determined from the type and number of care visits required by the clinical protocols. Laboratory tests and imaging studies were costed according to the Ontario Health Insurance Plan (OHIP) Schedule of Fees and Benefits. To estimate whether phase II trials are more costly than standard treatment, we determined the cost of four cycles of VP-16-cisplatin, a standard treatment for SCLC.
The total cost of performing the docetaxel study was $18443 for an average cost per case of $1317 and an average cost per treatment cycle of $683. The gemcitabine study cost more, due to the fact that the drug proved to be active against SCLC and more cycles of therapy were administered to a larger number of patients. Laboratory and administration costs were also higher, because of the drug administration schedule. The total cost of this study was estimated to be $64670 and the average cost per patient entered was $2230 with an average cost per treatment cycle of $898. In comparison, the estimated cost of four cycles of VP-16-cisplatin chemotherapy was $3948 or $987 per treatment cycle. The major cost drivers in the clinical trials were laboratory and imaging tests which made up 17 and 39%, respectively, of the costs of the taxotere study, and 29 and 27%, respectively, for the gemcitabine study. Data management costs contributed 21 and 13% of the total costs, respectively.
As the main cost drivers in these phase II clinical trials are laboratory and imaging tests, the cost of clinical trials could potentially be reduced by ensuring that only essential tests are required by protocol. Not surprisingly, the cost of conducting a trial of an active agent is greater than for an inactive agent, because more patients are treated and each patient receives more treatment. The implications for the per-case funding of phase II clinical trials are discussed.
Lung cancer is the leading cause of cancer death worldwide. Sex differences in lung cancer incidence and survival are known. Female sex is an independent good prognostic factor. Estrogens appear to play a key role in lung cancer outcomes. Accordingly, antiestrogen use may also influence survival in female non-small cell lung cancer (NSCLC) patients. In this study, we compared survival among antiestrogen users and nonusers. We performed a retrospective population-based study. Using the Manitoba Cancer Registry (MCR), we identified all women diagnosed with NSCLC from 2000 to 2007. The population-based Drug Program Information Network was accessed to establish which patients received antiestrogens. Demographic data (e.g., smoking patterns, stage, histology) were gathered from the MCR and by chart review. Survival differences between antiestrogen-exposed and not exposed groups were compared using multivariable Cox regression. Two thousand three hundred twenty women fit our patient criteria, of which 156 had received antiestrogens. Exposure to antiestrogens was associated with a significantly decreased mortality in those exposed both before and after the diagnosis of NSCLC (adjusted hazard ratio, 0.42, p?=?0.0006). This association remained consistent across age and stage groups. Antiestrogen use before and after the diagnosis of NSCLC is associated with decreased mortality. This supports previous evidence that estrogens may play a key role in the biology and outcomes of NSCLC and suggests a potential therapeutic use for these agents in this disease.
The incidence of brain metastases secondary to small cell lung cancer (SCLC) is about 35% and the treatment strategy of brain irradiation with respect to dose and fractionation is controversial. In order to evaluate treatment outcome of brain irradiation in SCLC patients with brain relapse, we retrospectively evaluated all patients treated with brain irradiation in the eastern part of Denmark from 1988 to 1992 (PCI patients excluded). During this 5-year period, 101 evaluable patients were included (44 females, 57 males) (median age 61 years; range, 39-75 years). Forty-four patients, of whom 43 were in extracerebral complete remission (CR), received extended course (EC) brain irradiation (> 45 Gy, treatment schedule > 4 weeks). Fifty-seven patients received short course (SC) brain irradiation (
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, pr. Akademika Lavrent'eva 8, Novosibirsk, 630090 Russia.
Challenges to implementation of an epidermal growth factor receptor testing strategy for non-small-cell lung cancer in a publicly funded health care system.
Data from seven recent randomized clinical trials have demonstrated that epidermal growth factor (EGFR) mutation status is predictive of improved progression-free survival and quality of life from first-line EGFR tyrosine kinase inhibitor therapy compared with platinum-based chemotherapy. We examined barriers to the initial implementation of a national EGFR testing policy in Canada.
Five laboratories across Canada underwent a validation and quality-control exercise for EGFR mutation testing using reverse transcriptase-polymerase chain reaction with financial support from the pharmaceutical industry for the initial 12 months. Oncologists registered patients with nonquamous histology for EGFR mutation testing using a Web-based platform. Basic demographics were collected including age, histology, sex, smoking status, and ethnicity. The decision to prescribe gefitinib was subsequently registered on the system.
Between March and December 2010, 2104 requests were received for EGFR mutation testing. Demographic details are as follows: adenocarcinoma (91.6%); Asian ethnicity (13.9%); female (58%); light/never smoker (41.3%); stage IV disease (87.1%). The number of tests requested each month ranged from 200 to 250. Mutation testing was conducted in 1771 of 2104 requests (84%). The median turnaround time for EGFR testing was 18 days (standard deviation 9.7). Gefitinib was prescribed in 302 patients (17.1%). The number of test requests dropped to 50 to 100 per month at the end of the initial 12 months.
There was rapid uptake of EGFR mutation testing into routine clinical practice in Canada. Uptake of EGFR mutation testing dropped substantially once funding from pharmaceutical industry was discontinued. There is a need for a national strategy to ensure resources are in place to implement molecular testing for new molecularly targeted agents.
