Multicentric survey on dose reduction/interruption of cancer drug therapy in 12.472 patients: indicators of suspected adverse reactions

Abstract

Antiblastic drugs have a high number of potential side-effects. Paradoxically, according to the National Network of Pharmacovigilance, the number of reported adverse reactions to these agents is proportionally lower than that registered for non antiblastic drugs. Critical phenomena such as treatment interruptions and significant dose reductions within the first two months of use may be indicators of adverse drug reactions. The aim of the present study was to increase our knowledge of pharmacovigilance to facilitate the actions taken to improve the risk-benefit profile of cancer drugs and, consequently, their safety. This retrospective observational survey was carried out on prescriptions from 1st January 2012 to 31st December 2012. Dose reductions of more than 10% during the first 90 days of therapy were considered as a surrogate indicator of an adverse reaction. Dose interruptions during the first 60 days of therapy were taken into consideration. Of the12,472 patients 1,248 underwent a dose reduction. The drugs that most often required a dose reduction were paclitaxel and oxaliplatin (17.4% and 17.3%, respectively), docetaxel (14.8%), carboplatin (15%), fluorouracil (10.7%) and, among oral medications, capecitabine (6.9%). Of the 1896 patients treated with the same drugs, 9.7% interrupted treatment. Patients required a lower dose reduction than that reported by other authors. Around 15% of cases underwent a 30% dose reduction within three months of starting therapy, indicating a possible adverse reaction. Constant monitoring of dose prescription and continuous training of medical and nursing staff are clearly needed to increase awareness of the importance of reporting adverse events.

Abstract

“…There is a paucity of data for chemotherapy delay rates for individual hospitals although there are data related to individual diseases. Gardini et al (2016) found that 9.7% of patients in their survey in Italy were affected by treatment delays. Pharmacists play an important role in patient care and their time to undertake audit and research is limited.…”

“…The more in-depth interviews revealed that patients had appreciated the opportunity to talk about their treatment and thought that discussion of information on drug doses with pharmacy was valuable. Gardini et al (2016) looked at this across a number of sites, reviewing retrospectively dose reductions and interruptions over a one-year period and reported a dose reduction rate of 10% and a discontinuation rate of 9%. Whilst there may be debate on the impact of delays on disease outcome there are economic consequences, these include wastage of pre-made chemotherapy, travel expenses for patients and also underused chemotherapy slots and waiting list considerations.…”

PIGN spatiotemporally regulates the spindle assembly checkpoint proteins in leukemia transformation and progression

“…2 C,D). This disparity between gene and protein expression may be linked to the post-translational regulation of MPS1 47 – 49 . Also, PIGN KO cells and cells ectopically overexpressing the intron-retaining mutant form of PIGN (MUT), presented with a significantly lower cell cycle frequency and mitotic index compared to wild-type PIGN (WT)-expressing cells (Fig.…”

Scrotal and Penile Erythrodysesthesia Associated with Neoadjuvant Capecitabine Chemoradiation

“…Possibly more significant than the agent itself is the drug formulation and administration schedule. The fact that the pegylated liposomal doxorubicin, liposomal daunorubicin, infusional 5-FU, and capecitabine have a stronger association with toxicities, of which PPE is included, than other drug formulations and administration schedules that do not result in such a sustained and prolonged tissue exposure would support this [2].…”