Summary of the 15th Annual Atlantic Canada Oncology Group Symposium

Abstract

The Atlantic Canada Oncology Group (ACOG) Symposium is an annual meeting. For the first 8 years it was held in Cornerbrook (NL, Canada) and for the last 7 years it has been held in Prince Edward Island (Canada). The target audience are medical and radiation oncologists from across the Atlantic Canadian provinces, but surgical oncologists, gynecologists, nurses, pharmacists, researchers, residents and other healthcare providers who work in oncology also benefit from the content presented at this meeting. The primary learning objectives are to promote cooperation among cancer programs in Atlantic Canada and to improve the quality of patients’ cancer care. Each year the meeting focuses on specific tumor sites, as well as other time sensitive topics. This year’s meeting focused on the management of genitourinary and gastrointestinal malignancies.

Keywords::

• ACOG
• bladder
• colorectal
• gastrointestinal
• genitourinary
• prostate
• renal

Genitourinary malignancies

Metastatic castrate-resistant prostate cancer

In the first presentation of the conference, Lori Wood, a medical oncologist at the Queen Elizabeth II Health Sciences Centre in Halifax (NS, Canada) addressed metastatic castrate-resistant prostate cancer (CRPC). The concept of ‘castrate resistant’ disease and the ongoing relevance of the androgen receptor signaling pathway at the level of the prostate cancer cells were highlighted. Therapeutic options that were available prior to 2004 were reviewed, including oral prednisone, antiandrogen withdrawal and mitoxantrone chemotherapy. Between 2004 and 2010 docetaxel chemotherapy was found to improve overall survival, quality of life and prostate-specific antigen response rates compared with mitoxantrone. Zoledronic acid was also shown to decrease skeletal-related events (SRE) in this patient population.

Since 2010, there has been an abundance of new therapeutic options in CRPC. Pre-chemotherapy data with sipuleucel-T showed a survival advantage (25.8 vs 21.7 months; p = 0.03) in a select untreated metastatic CRPC patient population with this ‘cancer vaccine’ [1]. Factors influencing how this therapy may fit into clinical practice in Canada were considered, including the feasibility of obtaining sipuleucel-T, and the cost on the Canadian publicly funded healthcare system.

New agents in the post-docetaxel setting were also discussed, including abiraterone, cabazitaxel and MDV3100. Abiraterone inhibits production of testosterone and dehydroepiandrosterone; Phase III results showed that patients who received abiraterone lived longer (14.8 vs 10.9 months; p < 0.001) [2], and updates on palliation, SRE end points and survival presented at the ASCO 2011 were reviewed. Phase III data comparing cabazitaxel to mitoxantrone in the second-line setting revealed a survival advantage (15.1 vs 12.7 months; p < 0.0001) [3]. MDV3100, a potent androgen receptor antagonist currently under investigation, is a promising agent post-docetaxel.

Wood then closed the prostate cancer session with the evidence surrounding denosumab, a RANK ligand inhibitor that shows an improvement in time to the first SRE event compared with zoledronic acid (20.7 vs 17.1 months; p = 0.0008) [4].

Muscle-invasive bladder cancer

As most patients with muscle invasive disease will die of distant disease, introducing chemotherapy in the perioperative setting may have significant potential advantages. The role of neoadjuvant and adjuvant chemotherapy was discussed by Scott North, a medical oncologist at the Cross Cancer Institute in Edmonton (AB, Canada).

In the last 20 years, there have been clinical trials exploring the use of cisplatin-based chemotherapy in both the neoadjuvant and adjuvant settings. The data has been difficult to interpret, especially in the adjuvant setting, owing to small studies, methodological flaws and conflicting results.

Scott North used the landmark meta-analysis to summarize the stronger data for neoadjuvant therapy; it included the large Medical Research Council trial showing an advantage to neoadjuvant chemotherapy with a 5% absolute survival improvement at 5 years [5]. The Southwest Oncology Group trial subsequently reported a survival advantage (77 vs 46 months; p = 0.06) [6].

Studies in adjuvant therapy have accrued smaller numbers and have many more methodological flaws. A meta-analysis of the reported studies shows a survival advantage of approximately 5–6% at 5 years; however, the poor-quality data used in the meta-analysis has to be considered [7].

The challenges delivering neoadjuvant and adjuvant chemotherapy in an older population with comorbidities was recognized. Discussion contrasted the approximately 5–6% improvement in overall survival at 5 years with potential toxicity.

A survey of Canadian genitourinary medical oncologists with regards to their perceptions and use of neoadjuvant chemotherapy was presented [8]. The majority of Canadian medical oncologists have extrapolated from the metastatic setting and use gemcitabine and cisplatin chemotherapy preoperatively; however, a few use high-dose methotrexate, vinblastine, doxorubicin and cisplatin. All agree that uptake of neoadjuvant chemotherapy by Canadian urologists and genitourinary oncologists is suboptimal, and it was emphasized that the majority of patients should see a medical oncologist to at least discuss the possibility of perioperative chemotherapy.

Metastatic renal cell carcinoma

Daniel Heng, a medical oncologist at the Tom Baker Cancer Centre in Calgary (AB, Canada), discussed the topic of ‘The ever-changing landscape of metastatic renal cell carcinoma’. Heng very eloquently and concisely reviewed the major advances with targeted therapy over the past 5 years. First-line targeted therapy options that are supported with Phase III, level 1 evidence include sunitinib, temsirolimus, pazopanib and bevacizumab plus interferon. In the second-line setting, there are data supporting both everolimus and axitinib as presented at the ASCO 2011 meeting. Axitinib was superior to sorafenib in terms of progression-free survival in previously treated patients [9]. Future research questions will address the optimal sequencing and dosing of these agents and how to best personalize the treatment of individual patients.

Heng reviewed important prognostic factors in patients with metastatic renal cell carcinoma in the pretargeted therapy era (the Motzer criteria) and in the new targeted therapy era (the Heng criteria) [10]. It is important to realize that not all patients behave the same in terms of their disease course and their response to treatment.

Safety of ambulatory care intravenous chemotherapy

Rachel White, a Human Factors Specialist at the University Health Network in Toronto (ON, Canada) closed the morning session with results and recommendations from a 2-year exploratory study regarding intravenous chemotherapy safety. The death of a patient due to a continuous infusion fluorouracil overdose was reviewed. Initially, after this incident, a root cause analysis of the event confirmed that there were many contributory system errors. Themes from a 2-year research project focusing on safety issues in a wide range of ambulatory intravenous chemotherapy environments were discussed, including:

• • Infusion chemotherapy delivery methods;

• • Pre-printed chemotherapy orders;

• • Drug preparation and verification;

• • The complexity and multiple steps required in timely chemotherapy delivery.

Simple steps to minimize error around these four themes were discussed. White also challenged all of us to identify areas of improvement in our own chemotherapy-delivered processes.

Gastrointestinal malignancies

Adjuvant colon cancer

The gastrointestinal sessions started with Scott Berry, a medical oncologist from the Sunnybrook Odette Cancer Centre in Toronto (ON, Canada). Berry’s talk addressed many of the challenges facing oncologists providing adjuvant therapy in colon cancer, including stage II (node negative) disease and elderly patients.

The role of adjuvant chemotherapy in stage II colon cancer is not well-defined. After reviewing ‘high risk’ features in stage II patients who may gain a greater benefit from adjuvant chemotherapy, including T4 lesions, obstruction/perforation, lymphovascular/perineural invasion, high grade and less than 12 regional lymph nodes harvested, Berry presented data from the large adjuvant QUASAR trial, in which 91% of subjects had stage II disease. A 3.6% absolute benefit in 5-year overall survival with 5-fluorouracil (5-FU) based adjuvant treatment was seen compared to observation [11]. By contrast, 6-year overall survival data among stage II subjects enrolled in the MOSAIC trial of adjuvant folinic acid, fluorouracil and oxaliplatin failed to show a significant benefit, even when the analysis was limited to high-risk stage II patients [12].

Berry reviewed the potential utility of the presence of microsatellite instability in decision-making in patients with stage II resected colon cancer who may be motivated to pursue treatment for a small potential benefit. There is evidence to suggest that patients whose tumors exhibit microsatellite instability do not benefit from 5-FU-based adjuvant chemotherapy, and may instead be harmed by its use; however, further study is required [13].

Localized rectal cancer

Next, the management of localized rectal cancer was addressed by Hagen Kennecke, a medical oncologist from the BC Cancer Agency in Vancouver (BC, Canada). Kennecke began with advances from the past two decades, highlighting the widespread adoption of postoperative chemoradiation during the 1990s. Later, refinements associated with lower toxicity and better locoregional control were seen, including preferentially treating in the neoadjuvant setting.

Kennecke then focused on the results from NSABP R-04, presented at the ASCO 2011. This relevant trial showed no significant difference between capecitabine and infusional 5-FU as radiosensitizers, while showing that oxaliplatin does not increase rates of pathological complete response, but is associated with greater toxicity.

Finally, future research directions and trials in progress were reviewed. After recognizing the advances that have been made in locoregional control, Kennecke identified distant relapse as a significant persistent problem in rectal cancer. Some strategies under investigation include administering systemic therapy before radiation and giving oxaliplatin in the adjuvant setting.

Metastatic colorectal cancer

With an original and intriguing approach, Scott Berry returned to the stage for a discussion of metastatic colorectal cancer therapy within an ethical and economic context. Beginning with a review of the evidence for the use of bevacizumab and EGF receptor inhibitors, medications which have increased the cost of treating metastatic colorectal cancer significantly, Berry then changed perspectives to present his personal research on Canadian and American oncologists’ perspectives on the value of these new therapies [14]. Interestingly, despite significant differences in their healthcare systems, oncologists from both countries held many similar views on the costs and cost–effectiveness of new cancer drugs and related health policies.

Summary

The meeting was a great success with a mix of many healthcare professions in attendance. A number of issues around the current management of genitourinary and gastrointestinal malignancies were discussed. It was also highlighted where we have a lack of knowledge and where research initiatives need to focus. The symposium will continue annually, with next year’s meeting being held from 14 to 16 June 2012 in Halifax (NS, Canada).

Financial & competing interests disclosure

Lori Wood is on the advisory boards for Pfizer, Novartis, Amgen, AstraZeneca and Janssen but receives no financial compensation. Stephanie Snow is on the advisory board for Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.