CancerCare Manitoba says no harm to patients underdosed on cancer drugs

Doctors with CancerCare Manitoba didn't tell 175 patients who were potentially underdosed on cancer drugs because they don't believe it caused anyone harm.

CancerCare Manitoba looked into its practices after a review by CancerCare Ontario found that excess medication remained in IV tubing for three specific drugs, resulting in a reduced dose delivery for 1,000 patients there. Those affected patients were notified of the situation.

"We felt that telling them that they were potentially underdosed doesn't necessarily help them in any way and it's going to cause a lot of anxiety. And we think that anxiety is unwarranted. Because we really don't think this has led to a reduction in the effectiveness of the drugs," said Dr. Piotr Czaykowski, chief medical officer for CancerCare Manitoba.

Regardless, CancerCare nurses will be using a new IV setup with a shorter line beginning Monday.

The three medicationspembrolizumab, nivolumab and panitumumab are classified as monoclonal antibodies: newer,potent drugs increasingly used to attack certain proteins, rather than directly on cancerous cells, as chemotherapy medications do.

Monoclonal antibodies most commonly to treat bladder and lung cancers and melanomas are typically given in higher concentration than chemotherapy drugs, so the amount of medication left in the IV line will cause a greater reduction in the dose delivered.

They also have a "much broader"therapeutic window than chemotherapy, said Czaykowski, meaning the amount of drug you get has a wide range to it which is both safe and effective.

"Knowing that these drugs have a wide therapeutic window, we think there is really no risk to the patients of harm," said Czaykowski.

The drugs are typically administered by nurses in a 50-millilitrediluent without a flush, as is routine practice with the administration of chemotherapy drugs in Manitoba, he said. Between 5-7 ml is left in the line following administration of both kinds of medication.

"If you have a 500 ml bag of chemotherapy and you don't give 5 ml of it, that's one per cent, that's not relevant. If you have a 50 ml bag and you don't give 5 ml that's 10 per cent, all of a sudden you have to start looking at that," he said.

Once the care teams weremade aware that the patients were likely receiving 15 per centless than the ordered dose of the monoclonal antibodies, Czaykowski said it was a "difficult decision made quickly"of whether to tell them.

Amount of drug 'not that fine-tuned'

"If these had been conventional chemotherapy drugs, there's no question we would be reaching out to the patients and seeing how they've done because our concerns would be both reduced responses and increased toxicity. Our decision here was based on the amount of this drug that we give is not that fine-tuned.It's typically accepted that a 10 per cent variance from the prescribed dose is completely acceptable. And nobody notifies patients of a 10 per cent difference."

The president of Pharmacists Manitoba said there still may be an impact on the patient.

"Not getting the full amount of medication, that can have adverse effects or you're not going to get better depending on what the medication is," said Barret Procyshyn, president of Pharmacists Manitoba.

"There can always be dangers of not receiving the complete dose of medication."

He said problems like this arise when there are multiple hands involved in ordering, preparation and administration of drugs.

"Better checks and balances need to be in place."

"And that's where we probably needed to focus a bit more attention than we did. Now that we're aware of this, it's clear to us that we have to change our process," conceded Czaykowski.

'Tremendous variability'

He said there is no way for doctors to measure whether there has been an impact to patients because of the "tremendous variability"to how cancers and patients respond to anti-cancer drugs of any sort.

"If you give the drug and someone does not respond, you can't say that's because you underdosed them. If you give the drug and someone has side effects, too much, you can't say you overdosed them," he said.

Two of these particular drugs are ordered for the patient based on the patient's weight, he said, but nivolumab has a fixed dose, meaning whether a patient is 50 kg or 100 kg, they'll get the same amount of the drug.

While CancerCareManitoba won't be approaching patients individually, there will be a process in place to answer their questions, Czaykowski said.

"It can be a challenge sometimes to weigh whether it's better to give people information when it isn't really particularly relevant. Or whether to accept that many patients would be alarmed by receiving this kind of information."

"We're confident that patients are not being put at risk and not in jeopardy."