ATLAS trial of adjuvant axitinib in patients with renal cell carcinoma: subgroup analyses with focus on axitinib dosing and racial groups.

BACKGROUND: The ATLAS trial, investigating adjuvant axitinib versus placebo in renal cell carcinoma (RCC), was stopped for futility at a preplanned interim analysis. We report subgroup outcome analyses by ethnicity, time on treatment, dose modification and toxicity. PATIENTS AND METHODS: Patient demographics, baseline characteristics, treatment duration and exposure and safety were analysed for Asian versus non-Asian patients treated with axitinib versus placebo. Disease-free survival (DFS) was analysed by ethnicity, treatment duration (≥1 versus <1 year), dose modification and adverse event (AE) grade. RESULTS: No DFS benefit was observed for Asian {hazard ratio (HR) 0.883 [95% confidence interval (CI) 0.638-1.220]} or non-Asian [HR 0.828 (95% CI 0.490-1.400)] patients treated with axitinib or placebo. Fewer Asian versus non-Asian patients were in the highest-risk group in axitinib (51.9% versus 72.3%) or placebo (51.5% versus 66.0%) arm. Highest-risk patients in both subgroups had no DFS benefit with either treatment. More axitinib-treated Asian versus non-Asian patients had dose reductions due to AEs (58.8% versus 46.0%; P = 0.028). Asian patients experienced more nasopharyngitis but less fatigue or asthenia than non-Asians. Among Asian patients, proteinuria, hypothyroidism, nasopharyngitis, and hypertension were more common in Japanese patients than Korean patients and more common in Korean patients than Chinese patients. Patients receiving axitinib >1 year versus ≤1 year did not have different DFS: HR 0.572 (95% CI 0.247-1.327); P = 0.1874. Compared with patients on stable axitinib dose, DFS was longer in patients with dose reduction [HR 0.458 (95% CI 0.305-0.687); P = 0.0001], whereas DFS was not different in those with dose escalation [HR 1.936 (95% CI 0.937-3.997); P = 0.0685]. DFS was not different in patients experiencing grade ≥2 versus <2 AEs within 6 months of initiating axitinib: HR 0.885 (95% CI 0.419-1.869); P = 0.7488. CONCLUSIONS: Asian versus non-Asian subgroup analysis revealed differences in AE experience and drug exposure. There were no DFS differences based on ethnicity or treatment duration, but axitinib dose reduction led to longer DFS.

Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: results from the phase III, randomized ATLAS trial.

Background: The ATLAS trial compared axitinib versus placebo in patients with locoregional renal cell carcinoma (RCC) at risk of recurrence after nephrectomy. Patients and methods: In a phase III, randomized, double-blind trial, patients had >50% clear-cell RCC, had undergone nephrectomy, and had no evidence of macroscopic residual or metastatic disease [independent review committee (IRC) confirmed]. The intent-to-treat population included all randomized patients [≥pT2 and/or N+, any Fuhrman grade (FG), Eastern Cooperative Oncology Group status 0/1]. Patients (stratified by risk group/country) received (1 : 1) oral twice-daily axitinib 5 mg or placebo for ≤3 years, with a 1-year minimum unless recurrence, occurrence of second primary malignancy, significant toxicity, or consent withdrawal. The primary end point was disease-free survival (DFS) per IRC. A prespecified DFS analysis in the highest-risk subpopulation (pT3, FG ≥ 3 or pT4 and/or N+, any T, any FG) was conducted. Results: A total of 724 patients (363 versus 361, axitinib versus placebo) were randomized from 8 May 2012, to 1 July 2016. The trial was stopped due to futility at a preplanned interim analysis at 203 DFS events. There was no significant difference in DFS per IRC [hazard ratio (HR) = 0.870; 95% confidence interval (CI) : 0.660-1.147; P = 0.3211). In the highest-risk subpopulation, a 36% and 27% reduction in risk of a DFS event (HR; 95% CI) was observed per investigator (0.641; 0.468-0.879; P = 0.0051), and by IRC (0.735; 0.525-1.028; P = 0.0704), respectively. Overall survival data were not mature. Similar adverse events (AEs; 99% versus 92%) and serious AEs (19% versus 14%), but more grade 3/4 AEs (61% versus 30%) were reported for axitinib versus placebo. Conclusions: ATLAS did not meet its primary end point; however, improvement in DFS per investigator was seen in the highest-risk subpopulation. No new safety signals were reported. Trial registration number: NCT01599754.

Axitinib versus sorafenib in advanced renal cell carcinoma: subanalyses by prior therapy from a randomised phase III trial.

BACKGROUND: In the AXIS trial, axitinib prolonged progression-free survival (PFS) vs sorafenib in patients with advanced renal cell carcinoma (RCC) previously treated with sunitinib or cytokines. METHODS: In post hoc analyses, patients were grouped by objective response to prior therapy (yes vs no), prior therapy duration (< vs ⩾median), and tumour burden (baseline sum of the longest diameter < vs ⩾median). PFS and overall survival (OS), and safety by type and duration of prior therapy were evaluated. RESULTS: Response to prior therapy did not influence outcome with second-line axitinib or sorafenib. PFS was significantly longer in axitinib-treated patients who received longer prior cytokine treatment and sorafenib-treated patients with smaller tumour burden following sunitinib. Overall survival with the second-line therapy was longer in patients who received longer duration of prior therapy, although not significant in the sunitinib-to-axitinib sequence subgroup; OS was also longer in patients with smaller tumour burden, but not significant in the cytokine-to-axitinib sequence subgroup. Safety profiles differed modestly by type and duration of prior therapy. CONCLUSIONS: AXIS data suggest that longer duration of the first-line therapy generally yields better outcome with the second-line therapy and that lack of response to first-line therapy does not preclude positive clinical outcomes with a second-line vascular endothelial growth factor-targeted agent in patients with advanced RCC.

Intermittent dosing of axitinib combined with chemotherapy is supported by (18)FLT-PET in gastrointestinal tumours.

BACKGROUND: We evaluated week-on/week-off axitinib dosing plus chemotherapy in patients with gastrointestinal tumours, including tumour thymidine uptake by fluorine-18 3'-deoxy-3'-fluorothymidine positron emission tomography ((18)FLT-PET). METHODS: During a lead-in period, patients received twice daily (b.i.d.) axitinib 7 mg (n=3) or 10 mg (n=18) for 7 days followed by a 7-day dosing interruption; serial (18)FLT-PET scans were performed before day 1 and on days 7, 10, and 14. Axitinib plus FOLFIRI or FOLFOX was then administered in 2-week cycles; axitinib was interrupted on day 10 of each cycle for 7 days. RESULTS: The maximum tolerated dose of axitinib was 10 mg b.i.d., in a week-on/week-off schedule, combined with FOLFIRI or FOLFOX. Common all-causality grade 3 adverse events were neutropenia (38%), hypertension (33%), and fatigue (29%). Of 21 patients, 2 (10%) had a partial response and 12 (57%) had stable disease. Following 7 days of continuous axitinib dosing, tumour (18)FLT uptake decreased -49% from baseline and recovered to -28% and -17% from baseline, respectively, after 3 and 7 days of axitinib interruption. CONCLUSION: Axitinib administered in a week-on/week-off schedule combined with FOLFIRI or FOLFOX is supported by (18)FLT-PET data and was well tolerated in patients with gastrointestinal tumours.

Patient-reported outcomes for axitinib vs sorafenib in metastatic renal cell carcinoma: phase III (AXIS) trial.

BACKGROUND: Axitinib demonstrated greater progression-free survival vs sorafenib in a phase III study of previously treated patients with metastatic renal cell carcinoma. Here, we report patient-reported kidney-specific symptoms and health status, measured by the Functional Assessment of Cancer Therapy (FACT) Kidney Cancer Symptom Index (FKSI) and the European Quality of Life self-report questionnaire (EQ-5D). METHODS: In all, 723 patients received axitinib (starting dose 5 mg twice daily (b.i.d.)) or sorafenib (400 mg b.i.d.). The FKSI-15, including the disease-related symptoms (FKSI-DRS) subscale, was administered on day 1 before dosing, every 4 weeks and at end of treatment (EOT)/withdrawal. Statistical methods included a mixed-effects repeated-measures model. RESULTS: At baseline, patients in both arms had relatively high mean FSKI-15 and FKSI-DRS scores, comparable to the general US population. Subsequent on-treatment overall mean scores were similar between axitinib and sorafenib, and there was no substantial decline during treatment. Scores substantially worsened at EOT, mainly due to disease progression. CONCLUSION: Patient-reported outcomes were comparable for second-line axitinib and sorafenib and were maintained at relatively high levels while on treatment, but worsened at EOT. As duration of treatment was longer with axitinib than sorafenib, time to worsening of symptoms can be delayed longer with axitinib.

Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours.

BACKGROUND: Axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, enhanced the efficacy of chemotherapy in human xenograft tumour models. This phase I study investigated the safety, tolerability, pharmacokinetics and antitumour activity of axitinib combined with chemotherapy. METHODS: A total of 42 patients with advanced solid tumours received a continuous axitinib starting dose of 5 mg twice daily (b.i.d.) plus paclitaxel (90 mg m(-2) weekly), docetaxel (100 mg m(-2) every 3 weeks) or capecitabine (1000 or 1250 mg m(-2) b.i.d., days 1-14). RESULTS: Common treatment-related adverse events across all cohorts were nausea (45.2%), hypertension (45.2%), fatigue (42.9%), diarrhoea (38.1%), decreased appetite (33.3%) and hand-foot syndrome (31.0%). There was one complete response, nine partial responses and seven patients with stable disease. Ten patients (23.8%) remained on therapy for >8 months. Paclitaxel and capecitabine pharmacokinetics were similar in the absence or presence of axitinib, but docetaxel exposure was increased in the presence of axitinib. Axitinib pharmacokinetics were similar in the absence or presence of co-administered agents. CONCLUSIONS: Axitinib combined with paclitaxel or capecitabine was well tolerated; no additive increase in toxicities was observed. Antitumour activity was observed for each treatment regimen and across multiple tumour types.

Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours.

BACKGROUND: This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours. METHODS: In all, 49 patients received axitinib 5 mg twice daily (b.i.d.) with paclitaxel/carboplatin or gemcitabine/cisplatin in 3-week cycles. Following determination of the maximum tolerated dose, a squamous cell NSCLC expansion cohort was enroled and received axitinib 5 mg b.i.d. with paclitaxel/carboplatin. RESULTS: Two patients experienced dose-limiting toxicities: febrile neutropenia (n=1) in the paclitaxel/carboplatin cohort and fatigue (n=1) in the gemcitabine/cisplatin cohort. Common nonhaematologic treatment-related adverse events were hypertension (36.7%), diarrhoea (34.7%) and fatigue (28.6%). No grade ≥3 haemoptysis occurred among 12 patients with squamous cell NSCLC. The objective response rate was 37.0% for patients receiving axitinib/paclitaxel/carboplatin (n=27) and 23.8% for patients receiving axitinib/gemcitabine/cisplatin (n=21). Pharmacokinetics of axitinib and chemotherapeutic agents were similar when administered alone or in combination. CONCLUSION: Axitinib 5 mg b.i.d. may be combined with standard paclitaxel/carboplatin or gemcitabine/cisplatin regimens without evidence of overt drug-drug interactions. Both combinations demonstrated clinical efficacy and were well tolerated.

CA 19-9 as a biomarker in advanced pancreatic cancer patients randomised to gemcitabine plus axitinib or gemcitabine alone.

BACKGROUND: Response assessment in advanced pancreatic cancer (APC) is difficult and predictive markers are needed. There are insufficient data on the value of carbohydrate antigen 19-9 (CA 19-9) and cytostatic-targeted therapies. Axitinib, a selective vascular endothelial growth factor (VEGF) receptors 1, 2, 3 inhibitor, may increase overall survival (OS) in APC. METHODS: We assessed serum CA 19-9, clinical outcomes and diastolic blood pressure (dBP) in APC patients receiving gemcitabine plus axitinib (Gem+A) or gemcitabine alone. RESULTS: In the total population (N=95), median OS was significantly longer in patients with baseline CA 19-9 values at or below the median than in those with values above it (12.2 months [95% confidence interval (CI), 8.6-16.6%] vs 5.0 months [95% CI, 3.9-5.7%]; P<0.0001). This also reached significance in the Gem+A arm (median OS, 12.5 months [95% CI, 8.6-16.6%] vs 4.9 months [95% CI, 3.6-5.6%]; P<0.0001). Patients with any dBP>90 mmHg had significantly longer OS than those who did not. However, there was no predictive significance of CA 19-9. CONCLUSION: Baseline CA 19-9 levels had prognostic value for OS, but caution is advised in interpreting CA 19-9 as a predictive biomarker for novel cytostatic agents such as VEGF-targeted therapies in phase II studies.

Telephone counseling as adjuvant treatment for nicotine replacement therapy in a "real-world" setting.

BACKGROUND: Physicians prescribing nicotine replacement therapy (NRT), or health plans covering NRT, often want their patients to receive adjuvant behavioral treatment. However, how to do that in a "real world" is unclear. This paper reports results from a public health program that uses proactive telephone counseling as support for physician advice and provides adjuvant treatment for NRT users. METHODS: Participants were NRT users (N = 8,832) who called the California Smokers' Helpline, a statewide cessation service that provides proactive counseling, one session before NRT use and multisessions after the smokers received NRT. After receiving NRT, some participants discontinued the counseling while others continued with follow-up sessions. A subset of the 8,832 participants (n = 664) was interviewed 13 months later for quitting status. RESULTS: After receiving NRT, 79% of the participants continued with counseling and received 4.2 sessions on average, while 21% of them received only one session. Overall, 82.8% of all participants made a quit attempt. Nicotine patch users were more likely to make an attempt than nicotine gum users (85.2% vs 66.3%), but the relapse probability was the same for these attempts. Those who received multiple counseling were more likely to make an attempt than those receiving single counseling (84.4% vs 77.1%) and were more likely to stay quit for 1 year (25.6% vs 16.1%). CONCLUSIONS: Proactive telephone counseling is a promising adjuvant treatment for NRT users in a "real-world" setting: a convenient referral service for supporting health plans or physicians who advise their patients to quit smoking.

Smoking cessation with and without assistance: a population-based analysis.

OBJECTIVE: To examine usage rates of smoking-cessation assistance and to compare the success rate of those who used assistance with the success rate of those who did not. METHODS: The data come from the 1996 California Tobacco Survey, a random sample of 4480 individuals (18 years or older) who tried to quit smoking in the 12 months before the survey. We calculated population estimates for demographics, smoking histories, rate of using assistance, and abstinence rates. RESULTS: One fifth (19.9%) of those who attempted to quit smoking used one or more forms of assistance: self-help, counseling, and/or nicotine replacement therapy (NRT). Heavy smokers were more likely to use assistance than were light smokers. Women were more likely to use assistance than were men, and usage increased with age. Whites were more likely to use NRT than were other ethnic groups. Overall, those who used assistance had a higher success rate than those who did not; the 12-month abstinence rates were 15.2% and 7.0%, respectively. CONCLUSIONS: Use of assistance for smoking cessation has increased over recent years, from 7.9% in 1986 to 19.9% in 1996. The use of assistance is associated with a greater success rate. Anti-tobacco campaigns in California and increased availability of multiple forms of assistance probably facilitated the use of assistance and successful quitting for those using assistance.

Has the California tobacco control program reduced smoking?

CONTEXT: Comprehensive community-wide tobacco control programs are considered appropriate public health approaches to reduce population smoking prevalence. OBJECTIVE: To examine trends in smoking behavior before, during, and after the California Tobacco Control Program. DESIGN: Per capita cigarette consumption data (1983-1997) were derived from tobacco industry sales figures. Adult (> or =18 years) smoking prevalence data were obtained from the National Health Interview Surveys (1978-1994), the California Tobacco Surveys (1990-1996), the Current Population Surveys (1992-1996), and the California Behavioral Risk Factor Survey and its supplement (1991-1997). Trends were compared before and after introduction of the program, with the period after the program being divided into 2 parts (early, 1989-1993; late, 1994-1996). MAIN OUTCOME MEASURES: Change in cigarette consumption and smoking prevalence in California compared with the rest of the United States. RESULTS: Per capita cigarette consumption declined 52% faster in California in the early period than previously (from 9.7 packs per person per month at the beginning of the program to 6.5 packs per person per month in 1993), and the decline was significantly greater in California than in the rest of the United States (P<.001). In the late period, the decline in California slowed to 28% of the early program so that in 1996 an average of 6.0 packs per person per month were consumed. No decline occurred in the rest of the United States, and in 1996, 10.5 packs per person per month were consumed. Smoking prevalence showed a similar pattern, but in the late period, there was no significant decline in prevalence in either California or the rest of the United States. In 1996, smoking prevalence was 18.0% in California and 22.4% in the rest of the United States. CONCLUSIONS: The initial effect of the program to reduce smoking in California did not persist. Possible reasons include reduced program funding, increased tobacco industry expenditures for advertising and promotion, and industry pricing and political activities. The question remains how the public health community can modify the program to regain its original momentum.

Are adolescents receptive to current sales promotion practices of the tobacco industry?

BACKGROUND: The tobacco industry increased the portion of its marketing budget for sales promotion to $2.5 billion in 1993. Although it claims not to target those under age 18 years, it is important to determine the extent to which adolescents are affected as participation may lead to smoking initiation. METHODS: California population surveys, conducted in 1993 among youth ages 12-17 years (N = 5,531) and in 1994 among both youth (N = 1,735) and adults (N = 4,170), asked questions regarding possession and willingness to use promotional items. RESULTS: In 1994, young adults (18-24 years) were the most likely to possess a promotional item (27.5 +/- 4.1, +/- 95% confidence limit). However, willingness to use an item was highest among those ages 15-17 years (35.4 +/- 3.4%) and was also high among those ages 12-14 years (24.4 +/- 2.7%). Among youth, ownership or willingness to use promotional items was more likely for boys, whites, those reporting below average school performance, and those smoking or susceptible to smoking. Youth ownership of promotional items increased from 1993 to 1994, as did the frequency of their obtaining items from coupons. CONCLUSIONS: Promotional marketing undertaken by the tobacco industry was effective in capturing the interest of adolescents, although actual acquisition was highest among young adults. The rapidly increasing interest in tobacco promotional items from 1993 to 1994 may soon translate into increased adolescent smoking rates.

Impact of the American Stop Smoking Intervention Study on cigarette consumption.

OBJECTIVE: To obtain an early estimate of the effectiveness of the American Stop Smoking Intervention Study (ASSIST). DESIGN, SETTING, AND PARTICIPANTS: Seventeen American states funded through ASSIST are compared with 32 others regarding per capita cigarette consumption from 1989 to 1995. California, which already had an extensive tobacco control programme, was omitted. ASSIST states were selected competitively (not randomly) based on their proposals' merit, state smoking prevalence, and geographical distribution. INTERVENTIONS: Comprehensive tobacco control programmes, emphasising policy interventions, were implemented in the ASSIST states beginning in 1993. MAIN OUTCOME MEASURES: Trends in aggregated per capita cigarette consumption and inflation-adjusted average price/pack of cigarettes in the intervention states were compared. Percentage change in per capita consumption is also compared with percentage change in inflation-adjusted cigarette price by state in each group from 1992 to 1994. RESULTS: Per capita consumption and inflation-adjusted cigarette price were nearly identical in both groups of states before 1993, when full funding for the ASSIST interventions began. However, by 1996 smokers in the intervention states were consuming about 7% less cigarettes per capita (P<0.05, beginning in 1994), and in 1994 the average price was over $0.12/pack higher in the intervention states. All but three states (all intervention) showed decreases in cigarette price. Nonetheless, 76% of the intervention and 55% of the comparison states showed some decrease in consumption despite decreases in price. The relationship between changes in price and consumption was considerably diminished in the intervention group. CONCLUSIONS: These interim results suggest that the ASSIST programme is associated with a substantial difference in tobacco consumption in a third of the United States, and that increased price from taxation may not be the only programme influence.

Addiction versus stages of change models in predicting smoking cessation.

Prospective data from the California Tobacco Surveys (n = 2066) were used to perform a critical test of the Prochaska et al. (1991) stages of change model. When the stages of change model was used as a stand alone predictor, smokers in preparation at baseline were more likely to be in cessation at follow-up than smokers in pre-contemplation at baseline (ORadj = 1.9). When stage membership was combined with baseline measures of addiction including smoking behaviors and quitting history, it was not a significant predictor of future cessation. A prediction equation that combined daily vs. occasional smoking, cigarettes per day smoked, life-time quits of at least a year, and quits of more than 5 days in the previous year discriminated smokers in cessation at follow-up of 1 to 2 years better than did the stages of change model. The area under the ROC curve for the equation based on addiction measures was 69.3% vs. 55.1% for the stages of change. Cessation rates ranged from 7.7% to 35.7% for the four-category addiction equation compared with 15.1% to 24.9% for stages of change model.

Telephone counseling for smoking cessation: effects of single-session and multiple-session interventions.

Smokers (N = 3,030) were randomized to receive 1 of 3 interventions: (a) a self-help quit kit, (b) a quit kit plus 1 telephone counseling session, or (c) a quit kit plus up to 6 telephone counseling sessions, scheduled according to relapse probability. Both counseling groups achieved significantly higher abstinence rates than the self-help group. The rates for having quit for at least 12 months by intention to treat were 5.4% for self-help, 7.5% for single counseling, and 9.9% for multiple counseling. The 12-month continuous abstinence rates for those who made a quit attempt were 14.7% for self-help, 19.8% for single counseling, and 26.7% for multiple counseling. A dose-response relation was observed, as multiple sessions produced significantly higher abstinence rates than a single session. The first week after quitting seems to be the critical period for intervention.

Is stage-of-change a useful measure of the likelihood of smoking cessation?

We compared two stage-of-change models that differentiate smokers by their level in the quitting process. The original 1983 model by Prochaska and DiClemente (1) divided smokers first by relapse status and then by intention to quit; their revised 1991 model (2) reversed the primacy of these factors. No published data justify whether the revision improves prediction of cessation. We used data from a population-based panel of 1,921 smokers interviewed in 1990 and 1992 for the California Tobacco Surveys. Model variables (quitting intention and recent quitting history) were used in a logistic regression to predict 30-day or longer cessation at follow-up and quit attempts made during the year preceding the survey. Predictive power of the revised model was not better than predictive power of the original model. New approaches to differentiating smokers on likelihood to quit should emphasize quitting behavior rather than intention to quit.

Cigarette smoking behavior and beliefs of Hispanics in California.

We examined the association between ethnicity and cigarette smoking beliefs and behavior in a 1990 random-digit dialing telephone survey of 3,164 Hispanic and 17,975 non-Hispanic white adults in California. Ethnic self-identification and native language were associated with the prevalence of current smoking in women but not in men. However, both male and female Hispanics smoked fewer cigarettes per day than their non-Hispanic counterparts. Hispanics who reported smoking in the past 12 months were more likely than non-Hispanics to have reached the action stage of cessation and to report an attempt to quit smoking. Spanish-speaking Hispanics were most likely to believe in the harmful effects of smoking, but also most likely to believe that smoking was not addictive, that they were not addicted to cigarettes, and that smoking is something everyone should try once. Cessation and prevention programs that target Hispanic populations must be especially sensitive to values and gender-specific acculturation processes that create a discrepancy between the desire to adopt the lifestyles of the dominant society and the recognition of the concomitant health-related risks.

Lower levels of cigarette consumption found in smoke-free workplaces in California.

OBJECTIVE: We examined the relationship between workplace smoking policies and smoking prevalence and cigarette consumption. METHODS: California residents were questioned by telephone with the 1990 California Tobacco Survey. All respondents (11,704) above age 18 years who were employed indoors were used. Respondents were asked about smoking status, workplace smoking policy, desire to quit, and smoking history. Logistic regression was used to determine the relationship of workplace smoking policy to smoking status, accounting for demographic variables. RESULTS: Prevalence of regular smokers was significantly lower in smoke-free workplaces than in those with no restrictions (13.7% vs 20.6%, P < .001). Continuing regular smokers in smoke-free workplaces smoked fewer cigarettes than those in workplaces with no restrictions (296 vs 341 packs per year, P < .001). More comprehensive smoking policies were associated with smokers more likely to contemplate quitting (P = .014). CONCLUSIONS: Employees in smoke-free workplaces have a lower smoking prevalence and, among continuing smokers, lower cigarette consumption than individuals working where smoking is permitted. We estimate cigarette consumption among employees indoors is 21% below that if there were no smoking restrictions in California workplaces. Furthermore, if all California workplaces were smoke-free, cigarette consumption among employees would be 41% below that if there were no workplace smoking restrictions, approximately a $406 million annual loss in sales to the tobacco industry. This study supports the hypothesis that smoke-free workplace policies are an effective public health measure for decreasing smoking prevalence and cigarette consumption among continuing smokers.

Public objections to environmental tobacco smoke.

METHODS. A randomly selected sample of Californian adults was surveyed by telephone to assess their knowledge, attitudes, and behaviors with respect to tobacco use and its control. The questions asked of this sample were whether they had recently (in the past 12 months) asked someone not to smoke in certain situations and whether they would ever consider doing such a thing. RESULTS. Results of the survey indicated that 59.1% of nonsmokers and 44.4% of smokers had asserted themselves within the past 12 months, while another 28.2 and 29.1% of the nonsmokers and smokers, respectively, indicated that they would consider asking someone not to smoke. Only 12.7% of the nonsmokers and 26.4% of the smokers indicated that they would not consider doing such a thing. Those more likely to object publicly to tobacco smoke are generally younger, are more educated, and have anti-tobacco attitudes related to either a specific health belief or social influence.

Projecting international lung cancer mortality rates: first approximations with tobacco-consumption data.

Cigarette smoking is strongly associated with later lung cancer; British data show a 0.83 correlation between tobacco consumption and lung cancer mortality 21 years later. We apply a simple tobacco-consumption model to data from countries in the Organization for Economic Cooperation and Development (OECD) to test the model in some nations and to roughly estimate future rates in others. This analysis provides some indication of the usefulness of the model, which could be applied to predictions for countries in which data are limited. This model predicts a US decline in male lung cancer mortality of approximately 25% by 2005 (a plausible prediction given recent declines in birth-cohort-specific lung cancer mortality rates); it also predicts reasonably well the start of documented declines in lung cancer mortality. According to this admittedly simple model, lung cancer mortality rates will increase in most European countries and Japan until 2000, but the twenty-first-century lung cancer epidemic will mostly occur in Asia.