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      The Cost of Treatment of Skeletal-Related Events in Patients with Bone Metastases from Lung Cancer

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          Abstract

          Purpose: Patients with bone metastases from lung cancer often experience skeletal-related events (SREs) including pathological fracture, spinal cord compression, hypercalcemia or pain requiring surgery, radiotherapy or opioid analgesics. These complications result in impaired mobility and reduced quality of life and have a significant negative impact on survival. The economic consequences of SREs in patients with lung cancer have not been examined. Methods: We conducted a retrospective analysis using a large US health insurance claims database to estimate the incidence and costs of treatment of SREs in patients with bone metastases of lung cancer treated in a naturalistic setting. Study subjects had ≧2 encounters with a diagnosis of primary lung cancer and ≧2 encounters with a diagnosis of metastases to bone. SREs were identified based on the occurrence on or after the date of first diagnosis of bone metastases, of (1) ≧1 encounter with a diagnosis of pathological fracture, spinal cord compression or hypercalcemia, (2) ≧1 bone surgery or radiotherapy procedure, or (3) the initiation of opioid analgesic therapy. Survival and costs of SRE-related care in patients with SREs were estimated using Kaplan-Meier methods. Results: We identified 534 patients with lung cancer and bone metastases, including 295 (55%) with ≧1 SRE. Radiotherapy (68%) and fracture (35%) were the most common SREs. Median survival after the first identified SRE was 4.1 months (95% confidence interval: 3.6–5.5 months). The estimated lifetime SRE-related cost per patient was USD 11,979 (95% confidence interval: USD 10,193–13,766). Radiotherapy accounted for the greatest proportion of cost (61%) by SRE type. Conclusion: The economic burden of SREs in patients with bone metastases of lung cancer is substantial. Intravenous bisphosphonates, such as zoledronic acid, which have been shown to prevent these events, may reduce these costs.

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          Most cited references6

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          Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer.

          Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. In a phase 2 study of irinotecan plus cisplatin in patients with extensive small-cell lung cancer, there was a high response rate and a promising median survival time. We conducted a multicenter, randomized, phase 3 study in which we compared irinotecan plus cisplatin with etoposide plus cisplatin in patients with extensive (metastatic) small-cell lung cancer. The planned size of the study population was 230 patients, but enrollment was terminated early because an interim analysis found a statistically significant difference in survival between the patients assigned to receive irinotecan and cisplatin and those assigned to receive etoposide and cisplatin; as a result, only 154 patients were enrolled. The median survival was 12.8 months in the irinotecan-plus-cisplatin group and 9.4 months in the etoposide-plus-cisplatin group (P=0.002 by the unadjusted log-rank test). At two years, the proportion of patients surviving was 19.5 percent in the irinotecan-plus-cisplatin group and 5.2 percent in the etoposide-plus-cisplatin group. Severe or life-threatening myelosuppression was more frequent in the etoposide-plus-cisplatin group than in the irinotecan-plus-cisplatin group, and severe or life-threatening diarrhea was more frequent in the irinotecan-plus-cisplatin group than in the etoposide-plus-cisplatin group. Irinotecan plus cisplatin is an effective treatment for metastatic small-cell lung cancer.
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            Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer.

            Between April 1985 and May 1988, we conducted a randomized study comparing two standard chemotherapy regimens with the same regimens given on an alternating basis in patients with small-cell lung cancer. The patients were randomly assigned to receive cyclophosphamide at a dose of 800 mg/m2 intravenously (IV) on day 1, doxorubicin at 50 mg/m2 IV on day 1, and vincristine at 1.4 mg/m2 IV on day 1 (CAV); cisplatin at 80 mg/m2 IV on day 1 and etoposide at 100 mg/m2 IV on days 1, 3, and 5 (PE); or CAV alternating with PE (CAV/PE). Each regimen was repeated every 3-4 weeks. Three hundred patients were entered in the study, and 288 of them were eligible for analysis (97 for CAV, 97 for PE, and 94 for CAV/PE). The response rates for PE (78%) and CAV/PE (76%) were significantly higher than the rate for CAV (55%), while the complete response rates were similar (14%, 16%, and 15%, respectively). Nine (23%) of 39 patients who failed to respond to the initial CAV regimen responded to PE when they were crossed over. In contrast, only one (8%) of 13 patients responded to CAV after failing to respond to the PE regimen, suggesting that these two regimens were partially non-cross-resistant. The response duration on CAV/PE was significantly longer than that with CAV (P = .004). The survival time with CAV/PE (11.8 months) was superior to that with CAV (9.9 months) (P = .027) or that with PE (9.9 months) (P = .056). In patients with limited disease, the survival in the alternating arm was significantly superior to the survival in the CAV arm (P = .014) or the survival in the PE arm (P = .023). The toxic effects were acceptable in all three chemotherapy regimens. These results favor the alternating chemotherapy over either standard chemotherapy, such as CAV and PE, although the differences are not dramatic.
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              Skeletal fractures negatively correlate with overall survival in men with prostate cancer.

              We assessed the correlation of skeletal fracture with survival in men with prostate cancer on chronic androgen suppressive therapy. A total of 195 consecutive patients on chronic androgen suppression for prostate cancer were evaluated for the history and type of skeletal fracture. Correlation with overall survival was performed via multivariate analysis. Of these 195 men 24 reported skeletal fracture since the diagnosis of prostate cancer. Median overall survival was 121 and 160 months in men without and with a history of skeletal fracture since the diagnosis of prostate cancer, respectively (p = 0.04). A history of skeletal fracture was retained as a negative predictor of survival on forward stepwise regression analysis (RR = 7.4, p = 0.007). Our results suggest that skeletal fracture in patients with prostate cancer is an independent and adverse predictor of survival. Consideration for screening men at greatest risk via bone mineral density measurements and initiating empirical skeletal therapies (bisphosphonates, estrogens and so forth) may be warranted. This recommendation awaits validation through prospective randomized trials.
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                Author and article information

                Journal
                OCL
                Oncology
                10.1159/issn.0030-2414
                Oncology
                S. Karger AG
                0030-2414
                1423-0232
                2004
                January 2005
                08 February 2005
                : 67
                : 5-6
                : 390-396
                Affiliations
                aPolicy Analysis Inc. (PAI), Brookline, Mass., bFox Chase Cancer Center, Philadelphia, Pa., cColumbia University College of Physicians and Surgeons, New York, N.Y., and dNovartis Pharmaceuticals Corporation, East Hanover, N.J., USA
                Article
                82923 Oncology 2004;67:390–396
                10.1159/000082923
                15713995
                d1580f16-6ec9-4688-b57d-bbfbf6a49d43
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 31 August 2004
                : 31 October 2004
                Page count
                Figures: 4, Tables: 1, References: 29, Pages: 7
                Categories
                Clinical Study

                Oncology & Radiotherapy,Pathology,Surgery,Obstetrics & Gynecology,Pharmacology & Pharmaceutical medicine,Hematology
                Lung carcinoma,Cost analysis,Secondary bone neoplasms,Retrospective study

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