New drug promises better treatment for cancer patients

One year into the Covid-19 pandemic, *judge Alex left a lush green golf course in Kampala, Uganda, fit as a fiddle and fulfilled to the bone. Golf had become his favourite game and an addictive fad.  His next business for that day was to go for a routine medical check-up, a tradition he has embraced since he turned 50 about 14 years ago.

It was in April and all he wanted that afternoon was to have his body checked. He was in high spirits, with the confidence of a tiger. Instinctively, he knew there was nothing wrong with his body and only hoped the doctor’s visit would not change that. It did.

All tests he took that day were passable except for one that the doctor didn’t quite understand and so the feedback that day was vague. He advised Alex that he needed further investigation. 

The doctor told him that cancer markers in his body had elevated. This meant there could be a possibility that he  could be having cancer, but markers alone are not sufficient to diagnose a patient for the disease.

Curious about the cancer markers, his doctor questioned him to find out whether he had lost weight, but his medical records showed that he had in fact gained five kilogrammes from the previous year and weighed 95 kilogrammes at the time of visit.

“The doctor asked me whether I was fatigued, but I told him I was just from playing golf. He probed further asking whether I had been feeling tired lately, and still, my answer was no. He thought that was quite strange because I didn’t have any symptoms, whatsoever,” says Alex.

Internal organs

The doctor let him go but put a caveat that it was prudent hey keenly observe him. He was asked to be back in a month.

In his next hospital visit, the doctor told him the cancer markers were even higher and that was a cue to carry on the medical examination for his body.

“He sent me to a CT-Scan (a computerised tomography scan that takes medical images for internal organs of our bodies), which revealed that there were lesions in the liver, but nothing was observed in the colon, and yet, the cancer markers were for the colon,” he tells Healthy Nation. 

The results from the CT-Scan were inconclusive and the next option was to send him to get a Magnetic Resonance Imaging (MRI) scan –a more sophisticated way of getting images from the body.

“The MRI scan also saw lesions in the liver, some which appeared as though they were cysts (an abnormal non-cancerous growth in the body) and his words, he said ; ‘your colon is clean, I didn’t see anything’ and that was strange to me,” he narrates.

To move on from the muddle arising from the results of the two scans, Alex was sent to a liver expert, who dismissed the possibility of him having liver cancer by just looking at the results from the scans he had done. He was asked to do a colonoscopy –an examination inside the colon (large intestine). 

“The doctor told me that should they not find a tumour in the colon, I should go home, because there was no explanation,” he says.

The colonoscopy revealed his colon had a tumour. In the process of colonoscopy, a biopsy was taken. This means that a tissue in his body was taken for further medical analysis.

The results from the biopsy came out and they found out that the tumour was cancerous.

Another scan, called a PET-Scan, was done after this revelation to discover if the cancer had spread to other parts of the body or it was just in the colon. 

This time he had to fly to another country, so he set off for Dubai in the United Arab Emirates. 

“I did a PET-Scan at the American Hospital in Dubai and they found that the cancer had spread to the liver and was in both lobes and so surgery was not an option. They advised me to start chemotherapy,” he explains. 

He had to delay the start of his chemotherapy when he went back to Kampala because a genetic test had to be done beforehand. His doctor from the Uganda Cancer Institute made a request to a laboratory in South Africa to analyse his biopsy blocks because the institute had no capacity to do that.

A fortnight later, the results came back and they found some parameters to be negative but some were positive. The analysis showed that he was positive of a unique gene called KRAS G12C. 

According to the Scientific Journal Nature, Kirsten rat sarcoma (KRAS) gene belongs to a member of the RAS family and its mutations are genetic drivers of multiple cancer types, especially colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and non-small cell lung cancer.

His cancer treatment journey began in July 2021, at stage four.

He had 11 cycles of chemotherapy to make his health better at every stage. 

“After 11 cycles, I was too exhausted with chemotherapy and I didn’t want to take the 12th one. I went for another scan and they didn’t find anything. Apparently, the cancer had cleared both in the liver and the colon but the cancer markers remained high,” he tells Healthy Nation.

The doctors agreed to give him a two-month rest from chemotherapy after which he would get a review and then be put on maintenance chemotherapy. 

“I thought maintenance chemo was going to be easier, like a tablet or something, but it was not any different. It is only that I was being given fewer drugs than the previous cycles. The side effects were unbearable,” he says.

“Nothing seemed to change and my doctor said there was no option, so I contacted my niece in Seattle, US to get another option,” he says.

He travelled to Seattle Cancer Care Alliance, now known as the Fred Hutchinson Cancer Centre. There, another genetic test, similar to the one that was taken in South Africa, was taken. 

“This new test revealed more details of the gene than the South African one. The doctors told me I was one of the few people in the world who had that specific gene, which could respond to a new drug that had just been approved for lung cancer but was in trial for colon cancer. They said it was doing even better for colon cancer patients,” he explains. 

He was told the drug could only be given to patients who did not have successful treatment options like chemotherapy, radiotherapy or surgery. So, he was put on another four cycles of chemotherapy and went back to Uganda with a detailed report. When he went to the Uganda Cancer Institute, there were some things that were lacking there and he says, “time was running out for me”. 

It was then that he came to Kenya, at the Nairobi Hospital, for another four cycles of chemotherapy, but there was no tangible progress. 

“The cancer was stable-ish. It had progressed a little, in fact, in the colon, they couldn’t see anything. As we were discussing with doctors at the Nairobi Hospital the next time, I reminded them of my genetic results and so they referred me to Aga Khan Hospital, where a new trial on a new drug was being undertaken,” he explains.

It is at the Aga Khan University Hospital’s Clinical Research Unit that Alex became a lucky man who would potentially revolutionise cancer treatment globally.

A series of tests were taken at the hospital to confirm whether the results at Seattle were the same as what they had. It took two weeks and he was found eligible for that treatment on trial.

Prof Saleh Mansoor, director of the Cancer Centre at the Aga Khan University Hospital, tells Healthy Nation that about 17 cancer patients were tested and only Alex had a mutated gene from KRAS called KRAS G12C.

He explains that all human cells have a gene called KRAS that serves as an important regulator to signal pathways responsible for cell proliferation, differentiation and survival. Should a mutation occur in a KRAS gene, it may allow cells to multiply out of control, and it may cause cancer.

The study, which is the first in Africa, is being also conducted in eight other countries globally and Kenya, specifically AKUH’s Clinical Research Unit, is one of the trial sites.

“This is a Phase 1b of the trial and we are testing how much dose is well tolerated for patients who have the KRAS G12C  gene. This gene is present in many cancers and it is already approved for lung cancer but a different molecule looks similar. However, this study is for any cancer that has that gene,” he explains.

“This study is for people who have failed other therapies because it is a new molecule. Alex, for instance, has tried chemotherapy but his treatment did not yield better results.  We have known this mutation for about five to seven years, but we did not have a solution to it. It is through research that we can now have a solution. 

“The goal of the study is to find out if the new drug can be used in the treatment for all cancers. If it works, we will then compare to gauge if it is better than the existing conventional forms of treatment in the subsequent phases, which will also look into efficacy.”

But how really does this drug work?

“What we know so far is that the drug blocks and inactivates the tumour so that it does not multiply. In the past, we even had drugs that damaged the DNA of the tumour. The drug therefore works by blocking a specific gene that is responsible for the creation of this tumour,” says Prof Mansoor.

The drug uses a field of science called precision medicine, which Prof Mansoor explains that it is a branch of medicine that targets a specific part of your body causing the disease such as genes, or proteins. Precision oncology, unlike the conventional one, is looking at the genetic makeup of the tumour and treating the patient to block that gene.

“This is the beginning of the future of cancer treatment. It doesn’t matter what type of cancer you have, in precision medicine, we will treat you for the gene that is causing the cancer. So there will be a time where doctors can identify cancer cells just by drawing blood and then test for the mutation of the cancer cells then pick up a drug that blocks the mutation,” he says. 

Prof Mansoor is hopeful that in about 10 years, patients may not need a mammogram for breast cancer, or colonoscopy to test for colon cancer. Instead, a simple blood test may soon help in telling both the cancer type, mutation of the gene in the tumour and eventually treat the patient. 

Kenya, however, has no capacity to test for the gene, so the blood has to be sent abroad for testing.

About the gene

What then is this gene, and how is it tested?

“We have 46 chromosomes in our bodies, in two pairs ; one from the father and the other from the mother. That is the genetic make-up of the body. In our bodies, our hair may have the same genes as our nails, but in the hair certain genes are told to be quiet so that you can make hair, but in the nails the genes activate,” he explained. “We can now sequence in a machine the genetic make-up of every cell and every tumour. It is called the Next-gene sequence machine. It looks like a small refrigerator. You then need a computer to decide how different it is from the normal cells,” he adds.

The patient will take the drug as long as it is working. 

The tumour is smart, it may try to escape, so research has to go on in order to block other mutations.

“It is a targeted missile against the enemy,” says Prof Mansoor.

Sehrish Rupani, the study coordinator and Clinical Research Nurse manager at Aga Khan University Hospital, tells Healthy Nation that the trial is the first in humans. “It is an oral drug targeting the gene. Once a patient is found with the specific gene; KRAS G12C, a criteria called inclusion-exclusion is done but first, the cancer type also has to be established. There is a list of items that a patient has to fulfil before consideration,” she says.

One of the recommendations, Sehrish says, is that a patient should have failed one line of treatment such as chemotherapy. 

“This patient (Alex) has received three lines of therapy before, he is progressing from the recent scan and has an advanced stage of cancer. He also fulfilled the required criteria, which is why he is the first one to be tried in the country,” she says.

“Since it is the first in humans, we really have to monitor the patient for adverse events and for any untoward effects, give him education on what he should expect and we have to have weekly meetings to update the team on how he is,” she adds.

Some of the side effects expected are nausea, vomiting and diarrhoea. At the moment, the dosage of the drug is about 400 milligrammes. 

A week after taking the drug, Healthy Nation visited Alex in hospital and the clinicians attending to him noted improvement in his cancer markers. He  experienced some side effects such as fatigue and nausea. “It has been a journey, I don’t know what the future holds, nobody knows, science is science. The good thing with science is that it is true, whether you believe in it or not,” he says.

“The doctors have told me they are confident that this medication should be able to help me and considering it is a trial, and it is free, then I have to believe in the science,” he adds

Should the drug be approved for use after all the phases of the clinical trials are done, Prof Saleh asks the Ministry of Health through the Pharmacy and Poisons board to be receptive to the drug as it will save lives. “If these drugs are successful, they are lifesaving for our patients, and improve their productivity. We should support this kind of research and invest in it. More importantly, the ministry should advocate for patients to come to hospital for early detection of cancer so as to be treated early,” he says.

“We are contributing new knowledge to the world. Everything we have now for treating cancer was tested in someone before. It will only be fair if regulatory agencies will be more receptive to research in the country,” he adds. 

Prof Mansoor now asks cancer patients who wish to be part of the study to present themselves and should they be lucky like Alex to have the KRAS G12C.  gene, then they will be among the first patients to use the drug.

“I want a supermarket of people to come for the clinical trials, this drug may be what they need,” he says. 

The name has been changed as requested by the patient for confidentiality. 

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