What we learned on June 5, 2004
Julia Draznin Maltzman, MD
Abramson Cancer Center of the University of Pennsylvania
The American Society of Clinical Oncology meeting was a wealth of information today. The take home message of what saw yesterday is discussed below and organized by disease type. Detailed coverage of the abstracts can be found on OncoLink for CME credit.
A number of abstracts were presented with the unifying theme of trying to devise the safest and best initial therapy for follicular lymphoma. CHOP chemotherapy is now considered the standard of care. Oncologists have been trying to improve the odds on an already highly curable disease by combining conventional chemotherapy with new monoclonal antibody therapies. This year a number of abstracts were presented looking at combinations with a radioimmunoantibody drug called Bexxar. All trials presented showed an improved response rate and a very favorable toxicity profile, however follow- up is too short to really show a survival advantage. The progression free survival is excellent, however, more time is needed before we can assess overall survival.
A crucial CALGB and SWOG (South West Oncology Group) study is now ongoing that will compare the conventional six cycles of CHOP chemotherapy with Rituxan to six cycles of CHOP with Bexxar. We all eagerly await those results.
Prostate cancer certainly was the most widely discussed topic yesterday. An EORTC trial (EORTC 2291) evaluated the role of radiation therapy in patients with a high risk of local recurrence after definitive surgery for prostate surgery. A ten percent difference favoring radiation therapy was noted. Another poster looked at the role of bisphosphonates in the prevention of bony metastasis from this disease. It was noted that bisphophonates did not impact the symptoms from bony lesions, but in patients with known bone metastasis, seemed to benefit by delaying the progression of these crippling consequences of prostate cancer.
Another poster examined the risk of bone fracture with hormonal therapy for prostate cancer. It turns out that those patients receiving a GnRh antagonist, such as Lupron, will have a higher relative risk of fracturing long bones than those patients not receiving such therapy. The length of treatment seemed to also correspond to likelihood of fracture. This study only supported the notion that hormonal treatment for men with prostate cancer is not very dissimilar to menopause that women go through biologically.
A CALGB study examined the significance of the rate of rise of PSA. It is accepted and understood that a faster PSA rise implies a worse prognosis. However, it is unclear the significance a change in the rate of rise of PSA following therapy. This trial showed an association of an improved survival benefit if the rate of rise were to decelerate. However this is only an association and further studies need to substantiate this finding.
The biggest news in prostate cancer will be presented tomorrow at the plenary session when the SWOG 9916 trial will discuss a possible new standard of care in the treatment of prostate cancer.
There were a multitude of presentations on the new targeted therapies available today. Investigators examined their application to all sorts of GI malignancies including hepatobilliary, pancreatic, and gastric. These malignancies are uniformly lethal, thus well-tolerated, non-toxic therapies in these diseases are extremely desirable. None of the studies showed tremendous success, unfortunately. Many showed promise but more studies are needed prior to broad clinical application.
Adjuvant therapy for colon cancer was re-visited and the current issue of New England Journal of Medicine confirmed the need for multi-agent therapy in stage III disease. The NCCN endorsed the use of the FOLFOX regimen in stage III disease. For stage II disease there is still little consensus regarding the benefit of therapy. Some investigators contended that perhaps molecular markers should be used to elucidate which stage II colorectal cancer patients would benefit from adjuvant chemotherapy.
For metastatic disease the biggest questions were how to best deliver chemotherapy to patients - sequentially or simultaneously. Now that we have three excellent and powerful drugs that help us fight this disease: 5 Fluorouracil, irinotecan, and oxaliplatin, the schedule and order of their administration is a serious question. One study showed a higher response rate with the combination of all three agents, however at the price of higher toxicity. The overall survival was similar to a two-drug regimen and therefore not yet recommended for use for all new metastatic colorectal cancer.
Neoadjuvant therapy was discussed but no consensus was attained. One thing became clear is that there are many new complexities to the treatment of this disease as our armamentarium of the available therapeutics increases. The question of when to operate and with what type of surgery has become a complex issue that is beyond the scope a single doctor but should be a combined decision among the oncologist, the surgeon, and the patient.
As expected, the new agents in colon cancer received much attention at this meeting. Erbitux again was shown to have about 11% activity as single agent but doubled its potency when combined with irinotecan. EGFR expression was again shown not to be related to response rate and the notable skin rash can be taken as a surrogate of drug activity.
Avastin was not associated with bleeding when given with anticoagulation as was feared and was not associated with venous thrombi. There were a number of unexpected arterial clots noted with Avastin (myocardial infarctions and strokes) but the significance of this was not clear and more studies are underway. There were also no wound healing problems noted in these studies as was initially suspected with this compound.
Trials with the COX II inhibitor, Celecoxib, suggested that there might be a decrease in the neuropathy seen with oxaliplatin and the hand foot syndrome sometimes noted with 5-fluorouracil. However the speculation is that there may be a lower response rate in the tumor with this agent as well.
Gastric cancer was again shown to have a better response rate if three agents were used in combination. The recommendation seemed to be Taxotere, Cisplatin, and 5-Fluorouracil. Three drugs are more toxic than two, however, and to patients with poor performance status, two drug combinations should be considered. PET imaging was looked at for this disease and more studies will be presented today on this topic.
Investigators of Esophageal cancer suggested that there might be a benefit to neoadjuvant therapy over post op treatment. And the small molecule tyrosine kinase inhibitors (Iressa and OSI 744) did not appear to have any efficacy in this disease.
There was little new for the field of lung cancer presented yesterday. Metalo-protease inhibitors were again shown to be ineffective and are therefore unlikely to go forward in the drug development for lung cancer.
The combination of chemotherapy and novel targeted therapy were shown, in general not to be effective. There were eight trials combining chemotherapy with metalo-protease inhibitors, four looking at chemotherapy and EGFR tyrosine kinase inhibitors, and one trial examining chemotherapy with anti-sense protein kinase C, all of which were negative trials. It is conceivable that these studies are negative because the interaction of chemotherapy with these new agents may somehow be antagonistic, or that too few people benefited to make it statistically visible. However, some contend, that the reason for the multitude of negative clinical trials is that targeted therapies should be aimed at a targeted population of patients. If we could identify those who would benefit, even if that number is small, we can give them this combination and not expose the majority of patients to a regimen that is ineffective in their disease.
The biggest news in breast cancer came in the trial showing a survival benefit in combination chemotherapy for metastatic breast cancer. This announcement rivaled traditional views of metastatic breast cancer of sequential single agent therapy.
MRI were noted again this year to be more sensitive than mammography for the detection of small, non-palpable tumors, However, critics question the cost benefit for society as MRIs are expensive and lead to many, potentially unnecessary invasive procedures.
In women over the age of 60 with clinically negative lymph nodes, a study found that surgical exploration of the lymph nodes does not negatively impact survival and may in fact improve the quality of life with less lymphedema and post surgical complications. In a similar trial, sentinel lymph node biopsy was found to be associated with less morbidity and better quality of life in all women.
Today's session should be as filled with new information and updates and OncoLink will be there to cover it.