An electronic non-interventional pharmacovigilance study of early-stage breast cancer patients on adjuvant treatment with anastrozole (Arimidex^®)

Introduction

Methods

All patients received the treatment dose (1 mg/ day) of anastrozole. Electronic case report forms (uploaded on laptops given to participating centers) were used to increase the quality of collected data. The electronic case report forms (eCRFs) facilitated registration of data by physicians; the electronic records also reduced errors in recording information and increased the reliability of data. During the study, the treatment pattern of physicians to the patients was not interfered; only the data regarding adverse events, the patient compliance and satisfaction were collected.

After the first visits of the patients, patients were followed up at 3rd, 6th, 12th, 18th and 24th month and if the physician requested, an additional last visit was performed. During every visit, patient compliance with treatment was evaluated and adverse events were recorded.

To evaluate the patient compliance, four questions asked to the patients: I) When did the patient begin to use the drug?, II) How has the patient been using the drug?, III) Did the patient have difficulty in using the drug?, and IV) Has the patient ever forgotten to use the drug?.

In every visit, after recording the symptom evaluation part of the eCRF for each patient, patient reported AEs were also filled by the physician. An adverse event was considered to be drug related when fulfilled at least one of the following criteria: a) if there is a logical time lapse and sequence between the administration of the drug and the development of AE, b) if the known clinical condition of the patient cannot be logically explained by environmental and toxic factors or the other treatments applied to the patient, c) if AE disappears or decrease when drug is ceased (in the exceptional situations, like bone marrow suppression, the drug relation with AE cannot be ignored even though AE does not disappear when drug is ceased), d) if AE follows a known and likely response pattern for the suspected drug, e) if AE is appeared, when the drug is re-administered.

Results

Anastrozole treatment was terminated in 17 (1.9%) patients following identification of recurrence during the follow-up period. A total of 35 patient-reported AEs were recorded in 18 patients. The number of AEs during each visit was shown in Table 1. The AEs were joint and muscle pain (n=9, 1.0%), hot flushes (n=5, 0.6%), vaginal dryness (n=4, 0.5%), weight gain (n=3, 0.3%), somnolence (n=3, 0.3%), vaginal bleeding (n=2, 0.2%), nausea (n=2, 0.2%), skin eruptions (n=2, 0.2%), asthenia (n=2, 0.2%), dyspnea-cough (n=1, 0.1%), cholelithiasis (n=1, 0.1%), and hair loss (n=1, 0.1%) (Table 2). The physicians considered 5 AEs as drug related for 5 patients, 3 AEs as possibly drug related for 2 patients, and 3 AEs as non-drug related for 2 patients; however, the causality relationship between AEs and the used drug could not be assessed in 9 patients. Joint and muscle pain and hot flushes were definitely associated with the drug, whereas, the association of cholelithiasis, vaginal dryness, and vaginal bleeding with the drug was uncertain. Of 35 AEs, 16 were described as mild, 3 as moderate, and 16 as severe; however, two of them were serious AEs. In addition, no death occurred due to AE. Four patients (3 patients with severe AE and 1 with moderate AE) showed improvement of muscle and joint pain when the drug use was stopped. Symptoms were observed again only in one patient with muscle and joint pain when the drug was readministered.

Table 1: Number of AEs according to the visits

Table 2: Distribution of adverse events

Approximately 90% of the patients who attended the follow-up visits reported that they experienced no difficulties in taking the drug, while 82% and 88% of the patients reported that they took the treatment exactly as prescribed in 6th and 7th visits, respectively. At the end of the last visit, the physicians were questioned about the compliance of the patients. Treatment compliance was evaluated in 126 patients and was found to be very good in 50% (n=63), good in 32% (n=40), moderate in 9% (n=12), and weak in 9% (n=11) of patients, respectively. The drug tolerability was very high in 49% (n=61), high in 34% (n=43), moderate in 10% (n=12), and low in 7% (n=9) of patients, respectively. Joint and muscle pain, and hot flushes were evaluated by the investigator as being causally related to treatment; whereas, the association of cholelithiasis, vaginal dryness, and vaginal bleeding with the drug was reported to be doubtful.

Discussion

Conclusion

Acknowledgements
The authors thank E-Safe Study Group; Mehmet Artac, MD, Alper Akinoglu, MD, Haluk Alagol, MD, Mehmet Alakavuklar, MD, Hilmi Alanyali, MD, Necati Alkis, MD, Mustafa Altinbas, MD, Mehmet Altinok, MD, Sefik Atabekoglu, MD, Guven Atasoy, MD, Ayhan Aydin, MD, Ugur Berberoglu, MD, Cem Boruban, MD, Suleyman Buyukberber, MD, Celalettin Camci, MD, Omer Cengiz, MD, Hasan Senol Coskun, MD, Gokhan Celenkoglu, MD, Abdullah Cetin, MD, Cumhur Demir, MD, Fuat Demirelli, MD, Taner Demirer, MD, Binnaz Demirkan, MD, Ozlem Er, MD, Ali Riza Erinekci, MD, Melek Erkisi, MD, Turkkan Evrensel, MD, Erdem Goker, MD, Alp Gurkan, MD, Omer Harmancioglu, MD, Ayfer Haydaroglu, MD, Burhan Hazar, MD, Abdullah Igci, MD, Gokhan Kandemir, MD, Murat Kapkac, MD, Aziz Karaoglu, MD, Ragip Kayar, MD, Adnan Kaynak, MD, Timur Koca, MD, Savas Kocak, MD, Alparslan Mayadagli, MD, Berna Olcun Dernek, MD, Feyyaz Ozdemir, MD, Mustafa Ozguroglu, MD, Pinar Saip, MD, Taflan Salepci, MD, Iskender Sayek, MD, Ertugrul Seyrek, MD, Isil Somali, MD, Berksoy Sahin, MD, Meric Sengoz, MD, Cetin Sengoz, MD, Ali Ihsan Seran, MD, Gunay Tanlak, MD, Salim Basol Tekin, MD, Ercument Tekin, MD, Turgut Tufan, MD, Gunduz Tunc, MD, Serdar Turhal, MD, Erdem Tuvay, MD, Mehmet Turk, MD, Adam Uslu, MD, Zafer Utkan, MD, Mustafa Unsal, MD, Deniz Yamac, MD, Sinan Yavuz, MD, Ibrahim Yildirim, MD, Nurullah Zengin, MD, Alper Sevinc, MD, Mustafa Samur, MD for their contributions to the study. The authors also thank Omega CRO, who provided software development, monitorization, data management, statistical analysis of data and medical writing support funded by Astra Zeneca.

References