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	Editor’s Note
	Extraordinary Cases

"After 75 years and millions of dollars in grants being offered to doctors and scientists, you mean to tell me that no cure for cancer could be found? Maybe no one wants to see cancer cured because they will lose money."

- Audience Participant
Breast Cancer Patients' Perspectives Meeting
Miami, Florida, September 14, 2003

The seemingly rapid progress in clinical research for cardiovascular disease and HIV has added to the frustration of cancer patients and oncologists who are hoping to see quicker progress. One of my favorite questions for interviewees for a breast, lung, prostate or colorectal cancer CME program is, "Where do you think clinical research is likely to be in 10 years?" Invariably, the answer relates to targeted therapy and the identification of predictors of response to systemic agents.

Is this research focus a reason for hope or just more hype to keep angry critics like the woman quoted above in abeyance? Two cases presented in this program create a strong argument that perhaps current approaches to targeted cancer therapy may provide some of the answers we have pursued for so long.

Dr Charles Blanke describes a 40-year-old man with an end-stage, heavily pretreated gastrointestinal stromal tumor (GIST) who traveled across the country to participate in an early Phase II study of imatinib (Gleevec®) in a final desperate attempt at remission. Within weeks, a pelvic tumor that was causing severe bladder compression and intense pain requiring narcotics "melted away," and three years later, the cancer has yet to recur and the patient is doing extremely well.

Dr Patrick Flynn describes another patient whose clinical course provides intriguing hints of future progress in oncology. After the surgical removal of a primary colon cancer, this mother of two teenagers received the disheartening news that she had unresectable retroperitoneal lymphadenopathy.

Hoping to contribute to the well-being of future cancer patients, she sought participation in a clinical trial and enrolled in a study and was randomized to bevacizumab, 5-FU and leucovorin. Within months, the tumor was in complete remission. Currently, two years later, she is asymptomatic and continues to have no evidence of disease while still receiving bevacizumab.

Will oncology waiting rooms 10 or 20 years from now be filled with patients like these or will we continue to struggle with relatively toxic interventions that provide modest antitumor benefits? Clearly, targeted biologic interventions like imatinib and bevacizumab are the focal points of a great deal of clinical research, but perhaps the identification of predictors of response in the tissue or serum will be even more important than the discovery of new agents.

In the last issue of our series, Dr Norman Wolmark discussed the challenge of finding a predictor of response to bevacizumab. However, he noted that in the landmark clinical trial presented by Dr Herbert Hurwitz at the 2003 ASCO meeting, the addition of bevacizumab to IFL conferred a major survival advantage, even in the absence of a tissue target that predicted response.

Investigators often cite the example of trastuzumab in breast cancer to emphasize the critical role of predictors of response with targeted therapies. It is fascinating to consider that the pivotal breast cancer clinical trial by Slamon et al would not have demonstrated a survival benefit if the study had been done in unselected patients rather than in women with HER2-positive breast cancer.

It is pleasant to fantasize of a time in the future when most cancer patients will have clinical courses like the patients of Drs Blanke and Flynn. To accomplish this formidable task, clinicians and patients must continue their commitment to participate in clinical trials. Hopefully, cancer survivors will then be able to feel a sense of relief, rather than frustration, at the pace of cancer clinical research.

-Neil Love, MD

Select publications

Demetri GD et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002;347(7):472-80. Abstract

Hurwitz H et al. Bevacizumab (a monoclonal antibody to vascular endothelial growth factor) prolongs survival in first-line colorectal cancer (CRC): Results of a phase III trial of bevacizumab in combination with bolus IFL (irinotecan, 5-fluorouracil, leucovorin) as first-line therapy in subjects with metastatic CRC. Proc ASCO 2003;Abstract 3646.

Kabbinavar F et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2003;21(1):60-5. Abstract