Drug-Drug Interactions to Avoid in Patients With GI Cancer

Liam Davenport

July 08, 2020

To avoid potentially life-threatening drug-drug interactions in patients with gastrointestinal cancers, clinicians should avoid polypharmacy, but if that is not possible, they should be on the lookout for potentially dangerous combinations and should monitor for adverse events, warned a leading expert in the field.

Rachel P. Riechelmann, MD, AC Camargo Cancer Center, São Paulo, Brazil, was delivering a keynote speech during the ESMO 22nd World Congress on Gastrointestinal Cancer Virtual Experience on July 4.

One of the drug-drug interactions that can have a deleterious effect on patients with GI cancers is that occurring between proton pump inhibitors (PPIs), such as omeprazole, and chemotherapy regimens containing capcitabine, she said.

She cited clinical trial data showing that the use of PPIs can increase the risk for progression in colorectal cancer patients being treated with adjuvant CapeOx (capecitabine with oxaliplatin) or FOLFOX (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin). Further clinical trial data from the LOGIC trial show that PPIs have a significant effect on both progression-free and overall survival in HER2+ gastric cancer patients being treated with CapOx with or without lapatinib.

Commenting on the presentation on Twitter, Jose Fernando Moura, MD, PhD, Medical Oncology, Real Hospital Português, Recife, Brazil, agreed that it is better to avoid PPIs during chemotherapy for colorectal and gastrointestinal tumors.

https://twitter.com/fernandoonco/status/1279435883142418433?s=21

Benedikt Westphalen, MD, PhD, coordinator, molecular oncology, University of Munich Comprehensive Cancer Center, Munich, Germany, replied that the data presented by Riechelmann are "clearly interesting."

He added his own checklist of things to consider in regard to drug-drug interactions, including changes in drug levels, the effect on the microbiome, and gender differences.

https://twitter.com/benwestphalen/status/1279438394314174468?s=21

Previous studies, including many from Riechelmann's group, have indicated that potential drug-drug interactions occur in about two thirds of inpatients and in approximately one third of outpatients.

The frequency of clinically relevant drug interactions in oncology patients enrolled in clinical trials is "not that high," however, at between 3% and 17%, depending on the mechanism of interaction, she commented.

"But it should be zero, because all clinical trials have a list of combinations that should not be prescribed and drugs that should be avoided," she added.

There have been very few studies on the occurrence of drug-drug interactions in oncology patients in the real world, Riechelmann commented.

One study suggested that 4% of oncology deaths in hospitals were due to adverse drug reactions or interactions. Another study, conducted by Riechelmann's team, suggested that 2% of nonelective hospitalizations among oncology patients were for drug-drug interactions.

She said that common potential drug interactions in oncology involve the use of aspirin, warfarin, beta blockers, and corticosteroids.

She also singled out olaparib (Lynparza, AstraZeneca) as an interesting case: co-administration of drugs that act as CYP3A4 inhibitors or inducers can effect exposure to this drug; itraconazole significantly increases exposure, and rifampin significantly reduces exposure.

Avoiding Interactions

In conclusion, Riechelmann made a series of recommendations for avoiding dangerous drug-drug interactions in cancer patients, the first of which is to avoid polypharmacy in the first place.

She also suggested that high-risk patients, such as those taking many drugs and who have comorbid illness, should be screened for potential drug interactions, and attention should be paid to "dangerous" combinations.

Combinations to avoid include those of two drugs that each prolong the QT interval. These include quinolones, azithromycin, and clarithromycin.

"I think every one of us has to develop our own list of dangerous combinations" that should be avoided if possible, she said. If their use is necessary, patients should be informed of the potential risk and should be monitored closely for adverse events.

No funding for the study has been reported. The investigators have disclosed no relevant financial relationships.

World Conference on Gastrointestinal Cancer (WCGC) 2020: Keynote: Harmful Drug Interactions in GI Oncology. Presented July 4, 2020.

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