Observational Study of Incidence Rates of Esophageal Cancer in Women Taking Medications for the Prevention or Treatment of Osteoporosis (MK-0217A-352) - Full Text View

Purpose

This is a 2-phase retrospective database study, using both case-cohort and inception (intention-to-treat) cohort analyses to evaluate any association between oral treatments for osteoporosis and the risk of esophageal cancer in women.

Condition	Intervention
Esophageal Cancer Squamous Cell Carcinoma Adenocarcinoma	Drug: Alendronate Drug: Etidronate Drug: Ibandronate Drug: Risedronate Drug: Raloxifene

Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Retrospective
Official Title:	The Risk of Esophageal Cancer in Relation to the Treatment and Prevention of Osteoporosis in Women

Resource links provided by NLM:

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders Osteoporosis

Drug Information available for: Etidronate disodium Raloxifene hydrochloride Ibandronic acid Risedronate sodium Alendronate sodium Ibandronate sodium

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:

Percentage of Participants With Exposure to Study Drugs (Case-Cohort Analysis) [ Time Frame: Exposure to study drug at least 720 days before disease onset ] [ Designated as safety issue: No ]
To determine the use of study drugs (alendronate, etidronate, ibandronate, risedronate, and raloxifene) among female participants with esophageal cancer (cases) and a comparison subcohort, a case-cohort analysis was performed using women meeting criteria from the General Practice Research Database (GPRD, United Kingdom). Exposure to osteoporosis drugs administered 720 days before cancer onset was determined in cases and compared to contemporaneous assessments in a comparison subcohort matched by year of birth and membership in the GPRD on the case's onset date. Cases were confirmed and case onset dates determined by electronic algorithm (based on electronic medical record data) or by medical record review.
Number of Cases of Esophageal Cancer Per 100,000 Woman-Years (Intent-to-Treat Analysis) [ Time Frame: Up to approximately 7.3 years of follow-up ] [ Designated as safety issue: Yes ]
To assess the relative risk of esophageal cancer associated with osteoporosis study drugs (alendronate, etidronate, ibandronate, risedronate, and raloxifene), initiators of osteoporosis drugs and non-initiators (comparators, women sharing match criteria with the initiator) entered an inception cohort for every three-month period, beginning in the first quarter of 1996. Assignment to study drug exposure group remained fixed from the start of follow-up, analogous to an intent-to-treat analysis. The risk of esophageal cancer among initiators of study drug compared to non-initiators of study drug was estimated through calculation of a hazard ratio. For calculation of 721+ day hazard ratios, only esophageal cancer cases occurring at least 721 days from initiation of study drug were used. For calculation of 1441+ day hazard ratios, only esophageal cancer cases occurring at least 1441 days from initiation of study drug were used.

Enrollment:	684815
Study Start Date:	February 2010
Study Completion Date:	February 2012
Primary Completion Date:	February 2012 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Esophageal Cancer Cases Participants with any United Kingdom General Practice Research Database (GPRD) Medical code for esophageal cancer (cases). Cases were confirmed and case onset dates determined by electronic algorithm (based on electronic medical record data) or by medical record review.	Drug: Alendronate Other Name: FOSAMAX® Drug: Etidronate Other Name: DIDRONEL® Drug: Ibandronate Other Name: BONIVA® Drug: Risedronate Other Names: ACTONEL® ATELVIA® Drug: Raloxifene Other Name: EVISTA®
Comparison Sample (Case-Cohort) Participants who were matched to cases by age and membership in the GPRD on the case's onset date, and had not experienced any form of esophageal cancer or Paget's Disease and had not received oral or intravenous steroids or chemotherapy or radiotherapy, as indicated by GPRD codes.	Drug: Alendronate Other Name: FOSAMAX® Drug: Etidronate Other Name: DIDRONEL® Drug: Ibandronate Other Name: BONIVA® Drug: Risedronate Other Names: ACTONEL® ATELVIA® Drug: Raloxifene Other Name: EVISTA®
Non-treated Comparators Participants who did not initiate treatment of osteoporosis with a study drug
Alendronate Participants initiating treatment for osteoporosis with alendronate	Drug: Alendronate Other Name: FOSAMAX®
Etidronate Participants initiating treatment for osteoporosis with etidronate	Drug: Etidronate Other Name: DIDRONEL®
Ibandronate Participants initiating treatment for osteoporosis with ibandronate	Drug: Ibandronate Other Name: BONIVA®
Risedronate Participants initiating treatment for osteoporosis with risedronate	Drug: Risedronate Other Names: ACTONEL® ATELVIA®
Raloxifene Participants initiating treatment for osteoporosis with raloxifene	Drug: Raloxifene Other Name: EVISTA®

Eligibility

Ages Eligible for Study:	55 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

Women who have at least two years of experience in the GPRD and are 55 or older between 1996 and 2008; all cases of esophageal cancer were identified and matched to all women in the comparison sample (all women with same year of birth drawn from the random subsample of 25,000).

Criteria

Inclusion Criteria:

Cases:
- Women in the database aged 55 or older between 1996 and 2008 with diagnosis of esophageal cancer
Comparator Controls:
- Each case was matched to all women in the random subcohort of 25,000 who had the same year of birth as the case and were in the database at the time of diagnosis.

Exclusion Criteria:

Women with diagnosis of any other cancer or Paget's Disease or who have received oral or intravenous steroids before the index date

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01077817

Sponsors and Collaborators

Merck

World Health Information Science Consultants, LLC

Investigators

Study Director:

Alec Walker, MD, DrPH

World Health Information Science Consultants, LLC

More Information

No publications provided

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT01077817 History of Changes
Other Study ID Numbers:	0217A-352, EP02001.029, 2010_015
Study First Received:	February 26, 2010
Results First Received:	November 1, 2012
Last Updated:	March 14, 2013
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Adenocarcinoma
Adenocarcinoma, Mucinous
Carcinoma
Carcinoma, Squamous Cell
Esophageal Diseases
Esophageal Neoplasms
Osteoporosis
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Neoplasms, Squamous Cell
Gastrointestinal Diseases
Digestive System Diseases
Gastrointestinal Neoplasms

Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Risedronic acid
Ibandronic acid
Etidronic Acid
Alendronate
Raloxifene
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Calcium Channel Blockers

ClinicalTrials.gov processed this record on May 23, 2013