Just this one short word is enough to strike fear in the heart of anyone diagnosed with cancer. But Sunnybrook researchers are making strides toward a future where chemotherapy will be simpler, safer and highly effective – and its devastating side effects a thing of the past.
Photo Credit: Tim Fraser
Delaney Janhunen was approaching her 36th birthday when she discovered a lump in her right breast. "You feel invincible when you're young and then all of a sudden you have this wake-up call," says Delaney, a Kitchener, Ont., mother of three, who is now 42.
Living in St. Catharines, Ont., at the time, Delaney was diagnosed with HER2-positive breast cancer, an aggressive type associated with overexpression of HER2 receptors on the cancer cell. "We were shocked and devastated when we realized how aggressive it was," Delaney recalls. It was an "additional devastation" when she and her husband, Paul, learned the cancer had produced seven tumours in her liver.
The young family was turned upside down. Delaney's new reality became surgery and ongoing drug therapy to eliminate the cancer and prevent its return. It worked for about two-and-a-half years, but the HER2-positive cancer returned, this time appearing in her left armpit.
It wasn't surprising to Delaney that it came back – doctors had been telling her the odds of recurrence were high. But it was still a crushing blow: "I had started hoping and wondering and praying that I was actually cured."
Delaney had a back-up plan. Before the recurrence, an acquaintance who also had HER2-positive breast cancer told her about a promising drug clinical trial underway at Sunnybrook's Odette Cancer Centre. The drug was T-DM1, which is a novel combination of a targeted drug therapy (Herceptin) and a chemotherapy drug (DM1). The combination drug is effective at zeroing in and killing breast cancer cells, while producing minimal side effects.
TRIALS AND TRIBULATIONS
Delaney's oncologist wasted no time in contacting Dr. Sunil Verma, a Sunnybrook medical oncologist and the lead author of the international T-DM1 study, which included patients from 213 centres around the world. Delaney received her first T-DM1 infusion in September 2010. She continues to make the trek from Kitchener to Sunnybrook once every three weeks to get her 30-minute infusion. Her tumours quickly shrank and she now has no detectable cancer on her CT imaging. "It's been a miracle drug, that's for sure," she proclaims.
"Delaney is one of hundreds of people who gain access to leading-edge cancer drug treatments every year through the Odette Cancer Program's clinical trial activities," says Dr. Calvin Law, the program's interim chief. "These trials are carried out at our Odette Cancer Centre's newly renovated and expanded chemotherapy unit."
Sunnybrook researchers, such as Dr. Robert Kerbel, are also pushing the frontiers of cancer drug therapy by developing less toxic, unconventional chemotherapy drug strategies that can be combined with other drugs, including Herceptin and T-DM1.
Innovation in therapy isn't limited to the treatments themselves. Odette Cancer Program staff are continually focused on improving the patient experience through technological and process improvements.
For Delaney, being selected for the T-DM1 trial "was like winning the lottery. I was jumping up and down."
Most importantly, the drug has kept her cancer at bay, but also key for Delaney, her husband and kids (ages ranging between nine and 14) is that there have been very few side effects. "The fact that you don't lose your hair and you don't feel sick has been wonderful," Delaney reports, although she does experience dry mouth and occasional tingling in her fingers.
"These findings [the T-DM1 study] create the framework for a new direction for the treatment of cancers, and potentially for earlier stages of the disease." Dr. Sunil Verma, Medical Oncologist
Compare this to the side effects of the drug therapy she received when she was first diagnosed with cancer in 2007. She lost her hair, eyebrows and eyelashes, and experienced fatigue for a few days after every round of treatment. "Losing my hair was very difficult to go through," she recalls, "difficult for my kids, too, because up until then you can go through life and not show everybody that you're sick."
Results from the T-DM1 study were published in the prestigious New England Journal of Medicine in November 2012. "Women who received T-DM1 lived much longer, had fewer side effects and enjoyed a better quality of life compared to those who received standard chemotherapy," says Dr. Verma. "These findings create the framework for a new direction for the treatment of cancers, and potentially for earlier stages of disease, by improving the way chemotherapies can now be combined with targeted therapies."
Delaney feels fortunate to have been included in the trial. She's also pleased to have taken part in research that recently resulted in the widespread approval of the drug for women with HER2-positive breast cancer. "It's humbling to think I had a role in helping to bring this drug to women across Canada," she says.
LESS CAN BE MORE
On the opposite end of the cancer research spectrum, Dr. Kerbel is partnering with Israel's Dr. Yuval Shaked on preclinical studies to get a better understanding of why "less can be more" when it comes to chemotherapy.
Dr. Kerbel has spent nearly half of his 30-year career as a cancer biologist pioneering a treatment known as metronomic chemotherapy. Unlike traditional chemo – characterized by high doses of toxic anti-cancer drugs usually given every few weeks for up to five months – metronomic chemotherapy uses lower and less toxic doses that are delivered more frequently, even daily, over one or more years.
"Traditional chemotherapy remains one of the main treatment methods for cancer, yet it has considerable side effects," explains Dr. Kerbel, a senior scientist at Sunnybrook Research Institute (SRI) and the Canada Research Chair in Tumour Biology, Angiogenesis and Antiangiogenic Therapy. "For people with cancers that spread aggressively, standard chemo usually doesn't extend life expectancy very much. In preclinical research, my laboratory has developed quite effective metronomic chemotherapy treatments for aggressive metastatic cancers – used either on their own or in combination with drugs called angiogenesis inhibitors, which cut off the blood supply that feeds tumours."
Dr. Shaked, who worked in Dr. Kerbel's SRI lab as a postdoctoral fellow, is now an assistant professor with the Rappaport Faculty of Medicine at Technion (Israel Institute of Technology). He notes that metronomic chemo remains a niche treatment concept that needs further investigation to bring it into the mainstream. In particular, the medical oncology world needs a better understanding of the biological mechanisms the treatment uses to attack cancer cells.
Drs. Kerbel and Shaked will get these answers with their international research collaboration. Through a generous donation from Rena and Michael Buckstein, Sunnybrook Foundation and Israel Cancer Research Fund are partnering to fund this innovative Canadian-Israeli research project.
"We will study several aspects of how metronomic chemotherapy acts against cancer cells," says Dr. Shaked. "This includes whether this method can target the reactive host response usually found after conventional chemotherapy, thereby delaying tumour relapse, in addition to the ability of metronomic chemo to act against tumour cells that are usually resistant to conventional therapy."
Their research will bolster recent and ongoing human clinical trials of metronomic chemo. A large study in the Netherlands among colon cancer patients has provided the first clinical evidence of the treatment's promise, and there are several other large trials underway among metastatic breast cancer patients around the world.
STAND AND DELIVER
For the Odette Cancer Program, innovation in drug treatment extends beyond testing the newest drugs and developing leading-edge therapies. Improving the delivery of treatment is equally vital.
"In recent years, we've made important changes that have led to notable improvements in the scheduling of therapy and the patient experience," says Philomena Sousa, process specialist and manager at the Odette Cancer Centre.
One change was the development and implementation of the Chemotherapy Appointment Reservation Manager
(CHARM), software that has helped reduce the average treatment wait time. It has also cut the number of phone calls between chemotherapy unit and pharmacy staff by 80 per cent, thanks to CHARM's automated communication approval of patient drug therapy regimens.
"The software streamlines processes through electronic communication and is essential for a busy chemotherapy unit like Sunnybrook's, which delivers treatment to about 23,000 patients each year," explains Dr. Maureen Trudeau, Sunnybrook's head of medical oncology.
The complexity of cancer drug treatments continues to increase. There are more than 400 different treatments, which vary in duration from 15 minutes to eight hours, plus clinical trials that result in changing treatment protocols. CHARM improves efficiency by accounting for various factors, including blood work requirements, medication mix time, nursing preparation and teaching time, patient condition, treatment complexity and infusion time.
The latest improvement in the drug therapy patient experience at the Odette Cancer Centre is the addition of a screen in the chemo waiting area that confidentially displays real-time information on appointment status. The aim is to keep patients in the loop at all times.
For instance, patients can see when their medications are being prepared and know how close they are to being called into the treatment suite. "Having this information frees patients to move around much more," says Sousa. "They can go and grab a coffee if they want, rather than be glued to their seats."
Dr. Calvin Law, interim Odette Cancer Program chief, says innovation within Sunnybrook's drug therapy program is wide-ranging. "Our experts do it all. They test and provide access to promising therapies. They pioneer the treatments of tomorrow through fundamental research, and they improve how we deliver treatment to patients.
"In the end, it all comes down to improving people's lives."
Dr. Yuval Shaked (Left) and Dr. Robert Kerbel kerbel are partnering on preclinical studies on the potential of "less is more" cancer treatments.
MORE QUICKLY TO THE ATTACK
For people with advanced non-small cell lung cancer (NSCLC), time is particularly of the essence. The cancer, which accounts for approximately 80 per cent of all lung cancers, can spark a rapid decline in health.
That's why Sunnybrook has made changes that have resulted in these patients beginning drug therapy about three weeks sooner. Sunnybrook medical oncologist Dr. Parneet
Cheema and Dr. Simon Raphael, deputy chief of Anatomic Pathology at Sunnybrook, spearheaded the initiative and are now sharing their experience with other Canadian hospitals to improve care for lung cancer patients further afield.
Through collaboration by medical oncologists and pathologists, Sunnybrook now expedites crucial tests that detect genetic mutations relevant to NSCLC patients. "Having one of the two mutations – known by their acronyms EGFR and ALK – will influence the choice of treatment," says Dr. Raphael, "so the sooner the status is known the sooner care can get underway."
Starting treatment earlier allows patients to receive life-extending drugs sooner, before they are too sick to receive therapy. "By receiving personalized drug therapy, according to the results of these mutation tests," notes Dr. Cheema, "patients may gain much more time – in some cases years – and improvement in their quality of life.
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