Furore over Avastin injection, treatment for cancers, loss of sight

In recent times, the use of Avastin Injection has been shrouded in controversy. There are conflicting reports on whether the injection should be used for treating patients with severe eye problems or cancers.

In fact, the National Agency for Food and Drug Administration and Control (NAFDAC) said the indications for which it registered Avastin injection are metastatic colorectal cancer, metastatic breast cancer, advanced metastatic or recurrent non-small cell lung cancer, advanced and/ or metastatic renal cell cancer, ovarian cancer and cervical cancer.

But several published studies and literature reviews indicate that eye doctors use Avastin to treat several eye and retina diseases, like age-related macular degeneration (AMD). AMD is the leading cause of blindness in people over 50 years of age. AMD is caused by the breakdown of the central portion of the retina, called the macula (the highly sensitive part of your eye that works like the film in a camera).

However, Avastin was not initially developed to treat eye conditions. Based upon the results of clinical trials demonstrating its safety and effectiveness, Avastin was also approved as a chemotherapy drug by the United States Food and Drug Administration (FDA) for the treatment of metastatic colorectal cancer. As a condition of approval, the manufacturer produced a “label” explaining the indications, risks, and benefits. The label explains that Avastin works by blocking a substance known as vascular endothelial growth factor or VEGF. Blocking or slowing VEGF helps prevent further growth of the blood vessels that cancer needs to continue growing.

The recent controversy over the use of Avastin was stirred on June 3, 2019, when NAFDAC received a complaint from a concerned Nigerian that ten patients at the National Eye Centre, Kaduna lost their eyesight following administration of Avastin 100mg injection.

In response to the complaint, an investigation was immediately initiated by NAFDAC. The members of the team met and discussed with the Management of the National Eye Centre, Kaduna on June 3, 2019. The following facts were established:

•Avastin 100mg injection was administered on the ten patients at National Eye Centre, Kaduna.

•National Eye Centre, Kaduna used Avastin Injection to treat patients with severe retina or macular pathologies.

•The ten patients were recalled by National Eye Centre Kaduna for observation and management following their complaints.

•The indications for which NAFDAC registered Avastin injection are metastatic colorectal cancer, metastatic breast cancer, advanced metastatic or recurrent non-small cell lung cancer, advanced and/ or metastatic renal cell cancer, ovarian cancer and cervical cancer.

•Therefore, the use of Avastin injection at the National Eye Center was an off-label use, that is, it is not indicated on the label by the manufacturer or approved for treatment of eye ailments by NAFDAC

•Avastin 100mg injection manufactured by F. Hoffmann-La Roche, Kaiseraugst 4303 Switzerland is registered by NAFDAC with NAFDAC Registration Number A6-0123. Avastin 400mg injection manufactured by F. Hoffman-La Roche, Mannheim, Germany is also registered with NAFDAC Registration Number A6-0101.

According to NAFDAC, one packet of Avastin injection in stock at the hospital was taken for laboratory analysis to ascertain the quality of the product and the report of analysis revealed that the Avastin injection conforms to quality specifications.

The agency, however, implored health care providers to ensure that Avastin injection is used as indicated by the company and as registered by the Agency unless there is a future scientific review of the indication for the product.

Unfortunately, the events led to calls for the withdrawal of the drug by the Nigerian Senate who passed a resolution calling on NAFDAC to immediately suspend the use of Avastin injections in the country.

Critics say the Senate position is understandable as, in normal circumstances, any drug, suspected to have a serious adverse effect on the patients, is withdrawn pending the outcome of investigations by competent regulatory bodies. However, the Senate’s resolution came even before NAFDAC, who had already commenced investigation into the incident, released the report of its findings.

Then came the jury. In its report, NAFDAC placed the blame squarely on the off-label use of the drug.

Consequently, some medical experts led by a professor of medicine and the foremost clinical oncologist with the College of Medicine University of Lagos (CMUL)/Lagos University Teaching Hospital (LUTH), Dr. Francis Durosinmi-Etti, advised against the suspension of the drug in the country.

Duosinmi-Etti, who was also the pioneer Chief Medical Director of the National Hospital, Abuja, and a radiation oncologist with the International Atomic Energy Agency in Vienna, Austria, aligned with the findings of NAFDAC over the cause of the National Eye Centre, Kaduna saga.

On the off-label use of the drug, Durosinmi-Etti raised two very salient points – concentration and mode of usage. According to him, “I have read about its successful use in the US for eye treatment, and I am aware this is done using special concentrations, not like the concentration we use for cancer treatment…There was the same issue sometime back in America where investigation showed the error came from the syringe used in administering the drug.”

The renowned oncologist, whose practice in the field of oncology has spanned over 47 years, attested that since he has been deploying Avastin in the treatment of various types of cancers he has not recorded any adverse effect from the drug.

“It is a relatively new drug, licensed in America in 2004. You know before it comes to Nigeria it would take of course say seven years or so. It has not had an adverse effect during this short period I have used it,” he informed.

Durosinmi-Etti was of the view that the suspension of Avastin would be counterproductive as it is the cancer patients in Nigeria who are going to bear the brunt of this action.

“If banned, it will mean you have taken away one of the important tools of treating cancer in Nigeria. Prior to now, there were certain ways of using drugs, but in this modern-day, what we do is targeted therapy at the molecular level, and that is one role this drug plays in cancer treatment. It is one of the new innovations we rely on in curing cancer.”

The oncologist informed that Avastin attacks cancers by blocking the receptor sites and ensures that the cancer cells that tend to proliferate by forming very tiny vessels do not proliferate anymore.

“Cancers tend to proliferate by forming very tiny vessels and that’s what makes them survive, but this is a drug that blocks receptor sites, it is an anti-vascular endothelial receptor site, so it blocks this sites on them and then ensures those vessels do not proliferate any more. That is the way it actually ‘cures’ cancer,” said Durosinmi-Etti.

He added, “Avastin use should still be encouraged because if that is taken away, many of our cancer patients will be in trouble. It is reasonably affordable to our patients. You know cancer drugs are expensive. Some may cost N1 million. How many Nigerians can afford that? So, one of the drugs we manage is Avastin because our patients can still afford it relatively.”

Durosinmi-Etti was of the view that the government should rather work with other relevant stakeholders to unravel the cause of the Kaduna incident than an attempt to place an envelope ban on the drug. Like him, I think this is the only way to go to ensure that the ugly incidence does not repeat itself while ensuring that the cancer patients, who need the drug to manage their conditions with Avastin, do not lose out on the benefits the drug offers.