Vinorelbine in advanced non-small cell lung cancer. A pharmacoeconomic review.

Vinorelbine is a semisynthetic vinca alkaloid that is effective against advanced non-small cell lung cancer (NSCLC). Myelosuppression is the primary dose-limiting toxicity; vinorelbine is otherwise relatively well tolerated. Two studies assessed the cost effectiveness of vinorelbine with or without cisplatin based primarily on data from a phase III comparison with vindesine plus cisplatin. Survival and cost data from this study were supplemented with those from other sources. One model simulated total management costs for the 4986 patients diagnosed with stage IV NSCLC in Canada in 1992. The other applied US cost data to the outcomes from the phase III trial. Using vinorelbine monotherapy or vinorelbine plus cisplatin produced a survival benefit and net cost savings compared with best supportive care according to the Canadian model (and preliminary data from a third analysis, conducted in the US). In the Canadian analysis, incremental cost effectiveness for inpatient or outpatient vinorelbine plus cisplatin ranged from 7450 Canadian dollars ($Can) to $Can30,770 (1993 values) per year of life saved (YLS) compared with outpatient cisplatin plus either etoposide or vinblastine. Cost-effectiveness ratios for vinorelbine plus cisplatin in the US analysis (1994 values) were $US18,000 (vs cisplatin plus etoposide) and $US15,500 (vs cisplatin plus vindesine) per YLS [all inpatient administration]. Detailed pharmacoeconomic comparisons with other current standard regimens (e.g. paclitaxel plus either cisplatin or carboplatin) are not available. Sensitivity analyses suggest that the cost effectiveness of vinorelbine-based therapy is robust to changes in assumptions regarding efficacy and the cost of managing toxicity. Limitations of the available pharmacoeconomic data include the retrospective nature of the analyses, inclusion of data from sources other than the main phase III trial (e.g. those for best supportive care and some chemotherapy regimens), and exclusion of some costs for hospitalisation and/or management of toxicity. CONCLUSIONS: Although some limitations apply, the available data suggest that vinorelbine alone or in combination with cisplatin is cost saving compared with best supportive care for NSCLC, and that vinorelbine plus cisplatin is cost effective compared with some other combination regimens. The pharmacoeconomic placing of vinorelbine in relation to a number of other currently recommended first-line treatments for NSCLC has yet to be resolved, and data from ongoing multicentre phase III trials are awaited with interest. In the meantime, vinorelbine-based chemotherapy appears to be a suitable choice for first-line treatment of advanced NSCLC from both clinical and pharmacoeconomic perspectives.     

Paclitaxel: a pharmacoeconomic review of its use in the treatment of ovarian cancer.

Paclitaxel belongs to the group of antitumour agents called the taxanes. Its efficacy in advanced ovarian cancer has been established in large, randomised phase III clinical trials. When used in combination with cisplatin for first-line treatment of advanced ovarian cancer, it is superior to cyclophosphamide/cisplatin, with gains in median survival of around 1 year. Paclitaxel plus carboplatin has similar efficacy to paclitaxel plus cisplatin. There is now consensus that paclitaxel plus either carboplatin or cisplatin is the recommended first-line therapy for patients with advanced ovarian cancer. The particular combination employed may vary between institutions and geographical regions, although paclitaxel plus carboplatin is generally better tolerated (i.e. lower incidence of non-haematological adverse events) than paclitaxel plus cisplatin and is widely used in many countries. Paclitaxel is also used as monotherapy in second-line (salvage) treatment of ovarian cancer. Pharmacoeconomic analyses performed to date have primarily focused on first-line therapy comparing the combination of paclitaxel/cisplatin with cyclophosphamide/cisplatin. All studies incorporated clinical outcomes data, most commonly from the Gynecologic Oncology Group (GOG) 111 trial, showing a survival advantage for paclitaxel/cisplatin. These studies report incremental cost-effectiveness ratios (ICERs) ranging from $US 6395 per additional life-year gained (LYG) in Spain (1995/96 values) to $US 44,690 per additional progression-free LYG in France (year of costs not reported). Five studies were based in the US and Canada and these reported very similar ICERs of $US 13,135 (year of costs not reported) to $US 25,131 (1993 costs) per additional LYG. In all of these studies the incremental costs of paclitaxel/cisplatin therapy fall well within the commonly cited threshold limit of $US 50,000 for new therapies and compare well with incremental costs reported for other oncological and life-saving therapies. Patient preferences and quality of life are important issues due to the short survival of patients with advanced ovarian cancer. Two cost-utility studies reported similar incremental cost-utility ratios (ICURs). In the study based on US costs, the ICUR of paclitaxel/cisplatin treatment was US $18,200 per additional quality-adjusted life-year (QALY) [1995 drug costs]. In a Canadian study the ICUR ranged from 11,600 Canadian dollars ($Can) to $Can 24,200 (1996 costs) per additional progression-free QALY depending on the choice of second-line treatment. CONCLUSIONS: Paclitaxel used in combination with cisplatin offers survival and utility gains versus cyclophosphamide plus cisplatin, when used as first-line treatment in patients with stage III or IV ovarian cancer. The incremental cost for these gains is within the accepted range for healthcare interventions. However, pharmacoeconomic analyses of paclitaxel plus carboplatin--a combination widely accepted for use in women with advanced ovarian cancer and with clinical advantages over paclitaxel plus cisplatin in terms of ease of administration and tolerability profile--are currently lacking. Nevertheless, results of available pharmacoeconomic data support the clinical use of paclitaxel/platinum combinations, particularly paclitaxel plus cisplatin, as a first-line chemotherapy treatment option in patients with advanced ovarian cancer.     

Economic evaluation of gemcitabine alone and in combination with cisplatin in the treatment of nonsmall cell lung cancer

OBJECTIVE: To evaluate the cost effectiveness of gemcitabine in the treatment of nonsmall cell lung cancer (NSCLC). METHODS: Gemcitabine was compared with best supportive care and gemcitabine/cisplatin was compared with three standard chemotherapies and four other novel chemotherapy combinations. Costs and effectiveness measures were based on resource and outcome data from previously reported clinical trials. All direct costs associated with NSCLC treatment were included and adjusted to year 2000 values. PERSPECTIVE: UK National Health Service. RESULTS: Gemcitabine plus best supportive care was associated with an incremental cost per progression-free life year gained of pound sterling5228 compared with best supportive care alone. In comparison with standard chemotherapies, gemcitabine/cisplatin was associated with an incremental cost per progression-free life year gained of pound sterling1751 versus etoposide/cisplatin and cost per 1-year survival gain of pound sterling5681 versus mitomycin/vinblastine/platinum. Incremental cost per tumour response was pound sterling2032 relative to etoposide/cisplatin, pound sterling5169 relative to mitomycin/ifosfamide/cisplatin and pound sterling6240 relative to mitomycin/vinblastine/platinum. Compared with four novel (newer) combination chemotherapies gemcitabine/ cisplatin showed cost savings in each case, with the same or better outcome. Thus, gemcitabine/cisplatin showed improved cost effectiveness and dominance. Sensitivity analyses showed the results were robust to variations to the values of key parameters. CONCLUSION: Gemcitabine alone or in combination with cisplatin was assessed to be a cost-effective or cost-saving therapy when compared with best supportive care, standard chemotherapy regimens and novel chemotherapy combinations. Chemotherapy regimens containing gemcitabine therefore represent good value for money and efficient use of healthcare resources in the treatment of advanced NSCLC.     

Potential cost savings of oral versus intravenous etoposide in the treatment of small cell lung cancer

An economic analysis was conducted on a randomised multicentre study comparing the use of intravenous (IV) etoposide versus oral etoposide treatment regimens in patients with small cell lung cancer. 41 patients received cisplatin 100 mg/m 2 intravenously (IV) on study day 1 and etoposide 120 mg/m 2 IV on study days 1, 2, and 3 (IV regimen); and 42 patients received cisplatin 100 mg/m 2 IV and etoposide 120 mg/m 2 IV on study day 1 and 240 mg/m 2 orally (equivalent to 120 mg/m 2 IV) on study days 2 and 3 (oral regimen). The results of the study from which these data were extracted showed equal efficacy between groups. Based on a retrospective review of resource use in the clinical trial, patient healthcare costs were examined in the following areas: antineoplastic drugs, IV fluids, supplies used for chemotherapy administration, and chemotherapy administration procedure fees. The total cost per course of therapy was $US2002 for the IV regimen and $US1653 for the oral regimen. This represented a 17% savings for patients receiving the oral regimen.     

Paclitaxel and lung cancer: new preparation. No therapeutic progress

(1) Paclitaxel is now licensed, in combination with cisplatin, for the treatment of non small-cell lung cancer in patients not qualifying for surgery or radiotherapy. (2) The clinical file is relatively bulky but of mediocre methodological quality. (3) In one trial the cisplatin + paclitaxel combination was neither more effective nor better tolerated globally than cisplatin monotherapy at a higher dose. (4) The cisplatin + paclitaxel combination has also been compared with the cisplatin + etoposide and cisplatin + teniposide combinations, but showed neither greater clinical efficacy nor fewer adverse effects.     

Paclitaxel: a hope for advanced non-small cell lung cancer?

Recent studies have shown that paclitaxel (Taxol); Bristol-Myers Squibb Co., Princeton, NJ) is an active agent in the treatment of advanced non-small cell lung cancer (NSCLC). Early trials in patients with advanced NSCLC utilised a 24 h infusion schedule and reported objective tumour responses in 21 - 24% of patients. Shorter infusion schedules have equivalent efficacy, and combined results from 14 separate trials of single agent paclitaxel in advanced NSCLC show an overall tumour response rate of 26%. Alternative schedules of paclitaxel from the traditional regimen every three weeks are under active investigation, but it is premature to assess whether these will yield improved efficacy for patients with advanced NSCLC. A single multicentre randomised trial of paclitaxel versus best supportive care in advanced NSCLC showed a significant survival advantage for the chemotherapy arm. Two large randomised Phase III trials have shown that paclitaxel and cisplatin is modestly more effective than cisplatin and podophyllotoxin combinations. The addition of cisplatin or carboplatin to paclitaxel results in higher response rates than for each of the drugs as single agents, but it is unclear whether the combinations yield superior survival or quality of life compared to single agent paclitaxel, or to other paclitaxel-containing regimens.     

Therapeutic options in the treatment of multiple myeloma: pharmacoeconomic and quality-of-life considerations

A review of current treatment options in multiple myeloma is presented, including data on health-related quality of life and pharmacoeconomics. For induction chemotherapy, no combination of cytostatic drugs has been shown to be consistently superior to the simple cyclic oral treatment with melphalan and prednisone that has been available for 30 years. The total resource consumption and direct costs per patient treated with melphalan and prednisone is approximately $US10,000 (1995 values). As median survival is prolonged from less than a year in untreated patients to 30 to 36 months, this treatment must be considered cost effective. Interferon-alpha has a modest effect on progression-free and overall survival when added to chemotherapy regimens. However, the high cost and toxicity of this drug results in an unfavourable cost-utility ratio, estimated to be between $US50,000 to $US100,000 per quality-adjusted life-year gained. Clinical trials suggest that high dose chemotherapy followed by autologous stem cell support administered to patients who have achieved disease stabilisation or objective response to conventional induction chemotherapy, prolongs median survival by about 1.5 years. Preliminary cost-utility analyses suggest a cost per life-year gained of $US30,000 to $US40,000. Further potential improvements of this therapeutic modality are under way. Several bisphosphonates have been tested for the ability to prevent the skeletal complications of multiple myeloma. Monthly infusions of pamidronate have been shown in 1 randomised trial to significantly reduce the rate of skeletal complications. Unfortunately, the rapid and widespread acceptance of this therapy seems to preclude further prospective, placebo-controlled trials with cost-utility evaluation.     

Modelling the cost effectiveness of antidepressant treatment in primary care

The aim of this study was to estimate the cost effectiveness of nefazodone compared with imipramine or fluoxetine in treating women with major depressive disorder. Clinical decision analysis and a Markov state-transition model were used to estimate the lifetime health outcomes and medical costs of 3 antidepressant treatments. The model, which represents ideal primary care practice, compares treatment with nefazodone to treatment with either imipramine or fluoxetine. The economic analysis was based on the healthcare system of the Canadian province of Ontario, and considered only direct medical costs. Health outcomes were expressed as quality-adjusted life years (QALYs) and costs were in 1993 Canadian dollars ($Can; $Can1 = $US0.75, September 1995). Incremental cost-utility ratios were calculated comparing the relative lifetime discounted medical costs and QALYs associated with nefazodone with those of imipramine or fluoxetine. Data for constructing the model and estimating necessary parameters were derived from the medical literature, clinical trial data, and physician judgement. Data included information on: Ontario primary care physicians' clinical management of major depression; medical resource use and costs; probabilities of recurrence of depression; suicide rates; compliance rates; and health utilities. Estimates of utilities for depression-related hypothetical health states were obtained from patients with major depression (n = 70). Medical costs and QALYs were discounted to present value using a 5% rate. Sensitivity analyses tested the assumptions of the model by varying the discount rate, depression recurrence rates, compliance rates, and the duration of the model. The base case analysis found that nefazodone treatment costs $Can1447 less per patient than imipramine treatment (discounted lifetime medical costs were $Can50,664 vs $Can52,111) and increases the number of QALYs by 0.72 (13.90 vs 13.18). Nefazodone treatment costs $Can14 less than fluoxetine treatment (estimated discounted lifetime medical costs were $Can50,664 vs $Can50,678) and produces slightly more QALYs (13.90 vs 13.79). In the sensitivity analyses, the cost-effectiveness ratios comparing nefazodone with imipramine ranged from cost saving to $Can17,326 per QALY gained. The cost-effectiveness ratios comparing nefazodone with fluoxetine ranged from cost saving to $Can7327 per QALY gained. The model was most sensitive to assumptions about treatment compliance rates and recurrence rates. The findings suggest that nefazodone may be a cost-effective treatment for major depression compared with imipramine or fluoxetine. The basic findings and conclusions do not change even after modifying model parameters within reasonable ranges.     

Role of gemcitabine in the treatment of advanced non-small cell lung cancer: review of the main phase II and phase III trials

Marked advances in the treatment of non-small cell lung cancer (NSCLC) have been made thanks to new agents. Among these agents, gemcitabine appears to be a major compound in advanced stage NSCLC chemotherapy. To start with, several phase III trials (conducted in Europe and in the USA) studied the gemcitabine/cisplatin combination (GC): US study protocois compared GC to cisplatin alone, to the standard treatment (etoposide/cisplatin) or to platinum/taxane doublets; in these studies, as a result of treatment with GC, a higher survival rate was observed. A study conducted in Italy, which is undergoing analysis, observes GC versus paclitaxel/carboplatin versus cisplatin/vinorelbine. In addition, in newer clinical protocols, it was observed that gemcitabine combined with taxanes or with vinorelbine demonstrated efficacy at least equal to that of combinations with platinum analogs. Newer agents acting on epithelial growth factor are also undergoing evaluation.     

Sequence-dependent cytotoxicity of combination chemotherapy using paclitaxel, carboplatin and bleomycin in human lung and ovarian cancer

Combination chemotherapy for non-small cell lung cancer (NSCLC) and ovarian cancer typically consists of a regimen of a taxane such as paclitaxel and a platinum-containing agent. Bleomycin, which halts cell cycle progression at G2 phase, is an agent which might thereby increase taxane cytotoxicity. The goal of this study was to evaluate the effect of different paclitaxel-platinum or paclitaxel-bleomycin schedules on cytotoxicity in human NSCLC and ovarian cancer cells. The simultaneous combination of paclitaxel and carboplatin exhibited simple additivity in vitro, while sequential exposure studies indicated that carboplatin followed by paclitaxel produced greater than additive cytotoxicity using the isobologram analysis of combinatorial effects. In contrast, the simultaneous combination of paclitaxel and bleomycin consistently exhibited greater than additive effects indicating a potentially synergistic combination. Sequential exposure studies of bleomycin followed by paclitaxel produced similar synergistic findings. Experiments in SCID mice evaluating the combinations of paclitaxel and bleomycin supported the in vitro results, as significantly enhanced A549 lung tumor growth inhibition was observed when paclitaxel was administered 1 h after bleomycin. The synergistic activity shown by the combination of bleomycin and paclitaxel indicates a potentially beneficial novel combination for treatment of NSCLC and ovarian cancer.     

Cost effectiveness in Canada of a multidrug prepackaged regimen (Hp-PAC)+ for Helicobacter pylori eradication

OBJECTIVE: To assess the cost effectiveness of a multidrug prepackaged regimen for Helicobacter pylori, the Hp-PAC (lansoprazole 30mg, clarithromycin 500 mg, amoxicillin 1 g, all twice daily), relative to alternative pharmacological strategies in the management of confirmed duodenal ulcer over a 1-year period from 2 perspectives: (i) a strict healthcare payer perspective (Ontario Ministry of Health) excluding the patient copayment; and (ii) a healthcare payer perspective including the patient copayment. DESIGN: A decision-analytical model was developed to estimate expected per patient costs [1998 Canadian dollars ($ Can)], weeks without ulcer and symptomatic ulcer recurrences for the Hp-PAC compared with: proton pump inhibitor (PPI)-clarithromycin-amoxicillin (PPI-CA), PPI-clarithromycin-metronidazole (PPI-CM), PPI-amoxicillin-metronidazole (PPI-AM) and ranitidine-bismuthmetronidazole-tetracycline (RAN-BMT). MAIN OUTCOME MEASURES AND RESULTS: All PPI-based regimens had higher expected costs but better outcomes relative to RAN-BMT. From a strict healthcare payer perspective, PPI-CM ($Can 209) yielded lower expected costs than PPI-CA ($Can 221) and slightly lower costs than Hp-PAC ($Can 211). However, these 3 regimens all shared identical outcomes (51.2 weeks without ulcer). When the current Ontario, Canada, $Can 2 patient copayment was added to the dispensing fee, Hp-PAC yielded lower costs ($Can 214) than PPI-CM ($Can 216). CONCLUSION: From a strict healthcare payer perspective, Hp-PAC is weakly dominated by PPI-CM with an incremental cost effectiveness (relative to RAN-BMT) of $Can 5.77 per ulcer week averted. When the patient copayment is added to this perspective, Hp-PAC weakly dominates PPI-CM ($Can 5 per ulcer week averted). Regardless of perspective, Hp-PAC and PPI-CM differed by only $Can 2 per patient over 1 year and the expected time without ulcer was 51.2 weeks for both. More data on the clinical and statistical differences in H. pylori eradication with Hp-PAC and PPI-CM would be useful. This analysis does not in clude the possible advantage of Hp-PAC in terms of compliance and antibacterial resistance.     

Glycoprotein IIb/IIIa receptor therapy in percutaneous coronary intervention and non-ST-segment elevation acute coronary syndromes. Estimating the economic implications

In addition to efficacy and safety, cost is an important determinant of the use of glycoprotein IIb/IIIa (GPIIb/IIIa) therapy in patients with acute coronary syndromes (ACS) or undergoing percutaneous coronary intervention (PCI). In PCI, the average procurement cost of GPIIb/IIIa therapy ranges from $US400 to $US1500 (1999 values) per patient treated, depending on agent, dose and duration of infusion. Prospective economic substudies with abciximab and tirofiban have demonstrated subsequent cost savings that partially offset the procurement costs of the agents. The drug procurement costs per death or myocardial infarction (MI) prevented in PCI appear to vary from $US10,500 to $US37,000, depending on the agent. Abciximab has been proven to provide a survival benefit in the setting of PCI, including coronary stenting. Analyses of abciximab use yield cost-effectiveness ratios of $US2875 to $US14,765 per life-year or quality-adjusted life-year saved, which compares favourably with most widely accepted therapies. In non-ST-segment elevation ACS, drug procurement costs range from $US700 to $US1700 per patient treated, also depending on agent, dose and duration of infusion. Evidence of cost offsets from changes in subsequent resource utilisation are limited and seem contingent upon a conservative risk-stratification approach. Drug procurement costs have been calculated as $US32,000 to $US82,000 per death or MI prevented in the ACS trials. Cost-effectiveness ratios of $US16,000 per life-year saved for the US and Western European cohorts in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial are favourable. If these analyses prove correct, the cost effectiveness of GPIIb/IIIa receptor therapy for patients with non-ST-segment elevation ACS will also compare favourably with other widely accepted therapies in industrialised countries. More clinical and economic data are necessary to allow better selection of specific patients who will receive the most benefit from GPIIb/IIIa therapy in healthcare systems with limited resources.     

Cost effectiveness of paclitaxel/cisplatin compared with cyclophosphamide/cisplatin in the treatment of advanced ovarian cancer in Belgium

OBJECTIVE: To assess the economic impact of two polychemotherapy regimens for patients with advanced ovarian cancer from the perspective of the Belgian health insurance and financing system. DESIGN: An economic evaluation was integrated in an intergroup randomised controlled trial (EORTC 55931) in which patients were randomised to receive the new treatment of paclitaxel and cisplatin or the standard therapy of cyclophosphamide and cisplatin. Data on the use of medical resources were collected prospectively for the 231 European Organization for Research and Treatment of Cancer (EORTC) patients in the trial and costs were valued by using unit prices. The outcome for the economic evaluation was mean survival time as determined by the so-called restricted means method, with the time point of restriction fixed by statistical criteria. A correction of censoring of the cost data collected in the trial was also performed. MAIN OUTCOME MEASURES AND RESULTS: The paclitaxel and cisplatin group experienced a statistically significant improvement in mean survival time of 4 months, which was associated with an increase in the average total cost per patient of 6795 euros (EUR; 1998 values), when costs were assessed over the same period as the gain in mean survival time. This corresponds to a point estimate of the incremental cost-effectiveness ratio of EUR20 385 per life-year gained. The impact of uncertainty was assessed by using a bias-corrected and accelerated bootstrap method with 5000 resamples, and the final results of the analysis are expressed in terms of a cost-effectiveness acceptability curve. CONCLUSIONS: The present economic evaluation has shown that the substitution of paclitaxel for cyclophosphamide in the chemotherapy regimen for women with advanced ovarian cancer leads to a significant improvement in patient survival, which is associated with an increase in costs for the Belgian health insurance system.     

Economic evaluation of oral sumatriptan compared with oral caffeine/ergotamine for migraine

We conducted an economic comparison of oral sumatriptan with oral caffeine/ergotamine in the treatment of patients with migraine. Cost-effectiveness, cost-utility and cost-benefit analyses were conducted from societal and health-departmental perspectives. A decision tree was used. Utilities were assigned to health states using the Quality of Well-Being Scale. Simple and probabilistic sensitivity analyses were also carried out. From a societal perspective, using sumatriptan instead of caffeine/ergotamine resulted in an incremental cost-effectiveness ratio of -25 Canadian dollars ($Can) per attack aborted, an incremental cost-utility ratio of -$Can7507 per quality-adjusted life-year (QALY), and a net economic benefit of $Can42 per patient per year (1995 values). From the perspective of the health department, the incremental cost-effectiveness ratio was $Can98 per attack aborted, the incremental cost-utility ratio was $Can29,366 per QALY; the grade of recommendation based on past decisions regarding health technology for adoption into health insurance plans was 'moderate'. Sensitivity analysis showed that the results were robust to relatively large changes in the input variables. The incremental health benefits obtained from using oral sumatriptan rather than oral caffeine/ergotamine were achieved at moderately acceptable incremental costs, if past decisions on the adoption of other health technologies are used as a guide.     

Pharmacoeconomic analysis of empirical therapy with ceftazidime alone or combination antibiotics for febrile neutropenia in cancer patients

There is evidence to suggest that single-agent broad spectrum antibacterials may be cost-effective alternatives to combination antibiotics for the empirical management of febrile neutropenia in cancer patients. The objectives of the present study were 2-fold. The first objective was to compare the clinical effectiveness of ceftazidime monotherapy with that of 2 combination antibiotic regimens in cancer patients with febrile neutropenia. The 2 comparator regimens consisted of tobramycin plus piperacillin, either with (regimen 'CAP') or without (regimen 'AP') cefazolin. The second objective was to perform a cost-effectiveness analysis of the 3 regimens. Meta-analysis of randomised comparative trials between the 3 therapy groups was performed to determine the average overall response rate after 3 to 5 days of treatment. Seven clinical studies were selected for analysis. The overall incidence of adverse drug reactions (ADRs) was determined using the results of comparative and noncomparative studies. A comparative cost-analytic model was applied from a hospital perspective. The costs of primary therapy, hospitalisation, laboratory tests, routine patient care and treating ADRs were calculated, as were future costs. Monotherapy with ceftazidime was associated with an overall response rate of 63.5% and mean per-patient costs of $Can12,000 to $Can14,000. In comparison, regimen AP was associated with an overall response rate of 58.8% and mean costs of $Can13,000 to $Can16,000 per patient. The overall response rate in patients receiving CAP was 75.3%, and the mean cost per patient was $Can11,000 to $Can12,000. Thus, regimen CAP was the most cost-effective therapy from a hospital perspective.     

Irinotecan in cancers of the lung and cervix

Irinotecan is active as a single agent in advanced non-small cell lung cancer (NSCLC), with overall response rates (ORRs) of 13-32% reported in phase II trials. In the first-line treatment of stage III/IV NSCLC, phase II studies have suggested that the combination of irinotecan with cisplatin can achieve response rates of 29-75%, which is greater than achieved with older platinum-containing combinations. Neutropenia and diarrhea are the dose-limiting toxicities. In small cell lung cancer (SCLC), irinotecan alone has achieved ORRs of 16-47% in previously treated SCLC, which is higher than expected with oral etoposide. Studies with irinotecan in combination with cisplatin or etoposide have reported responses of up to 79%. Irinotecan is active in cervical cancer patients whose metastases are outside the area of previous irradiation (ORR 24%) and a major phase II/III study is currently comparing irinotecan as single agent or in combination with cisplatin against a reference cisplatin arm.     

From randomised clinical trials to clinical practice : a pragmatic cost-effectiveness analysis of Paclitaxel in first-line therapy for advanced ovarian cancer

INTRODUCTION: Paclitaxel plus cisplatin is considered to be the standard first-line therapy for advanced ovarian cancer. Previous to this study, economic data on this combination resulted from randomised clinical trials (RCTs). Therefore, the objective of this study was to compare the clinical and economic outcomes associated with paclitaxel-cisplatin (PC) and cyclophosphamide-cisplatin (CC) regimens using a pragmatic perspective based on daily clinical practice in a French university hospital. METHOD: A retrospective cost-effectiveness analysis, from the hospital-payer perspective, was carried out as a before-after case study in fifty-nine consecutive women with verified International Federation of Gynaecology and Obstetrics (FIGO) stage II, III or IV ovarian cancer treated between 1995 and 2000. Median overall survival (OS) was used as the primary endpoint. The quality-adjusted time was assessed by the quality-adjusted time without symptoms or toxicity (Q-TWiST) method. Direct medical costs were collected for each patient. Monetary values for French prices in the year 2000 were used and converted to US dollars using an exchange rate of USD 1 = 7 French francs. Several univariate sensitivity analyses were carried out varying unit costs, medical practices and administration of paclitaxel. RESULTS: The incremental cost of the PC regimen was USD 10,716 per patient. OS and quality-adjusted time were improved by 10.8 and 9.3 months with the PC regimen. The cost per life-year gained and per added QALY were USD 11,907 and USD 13,827, respectively. The robustness of the results was confirmed in sensitivity analyses. CONCLUSION: Our study suggests that PC may be a cost-effective regimen for advanced ovarian cancer in a French university hospital setting. We reported higher incremental costs and lower clinical benefits than RCT-based findings, suggesting that RCT-based findings were clearly balanced by our pragmatic approach based on clinical practices. Observational studies can provide complementary and balanced data for decision making.     

DNA-PK inhibition by M3814 enhances chemosensitivity in non-small cell lung cancer

A significant proportion of non-small cell lung cancer (NSCLC) patients experience accumulating chemotherapy-related adverse events, motivating the design of chemosensitizating strategies. The main cytotoxic damage induced by chemotherapeutic agents is DNA double-strand breaks (DSB). It is thus conceivable that DNA-dependent protein kinase (DNA-PK) inhibitors which attenuate DNA repair would enhance the anti-tumor effect of chemotherapy. The present study aims to systematically evaluate the efficacy and safety of a novel DNA-PK inhibitor M3814 in synergy with chemotherapies on NSCLC. We identified increased expression of DNA-PK in human NSCLC tissues which was associated with poor prognosis. M3814 potentiated the anti-tumor effect of paclitaxel and etoposide in A549, H460 and H1703 NSCLC cell lines. In the four combinations based on two NSCLC xenograft models and two chemotherapy, we also observed tumor regression at tolerated doses in vivo. Moreover, we identified a P53-dependent accelerated senescence response by M3814 following treatment with paclitaxel/etoposide. The present study provides a theoretical basis for the use of M3814 in combination with paclitaxel and etoposide in clinical practice, with hope to aid the optimization of NSCLC treatment.