Head and Neck continued...
Next presentation was by Dr. Langer who looked at the historical changing patterns in treatment for h/n in the Western Hemispere.
By the late 90's...chemo/RT became most common treatment.
Looked at age, race, sex,ethnicity, and stage of diagnosis(stage 3-4 most common)
Regarding survival advantage...Caucasian and African American about the same...but Asian population had notably better survival(slides were going so fast, I couldn't transcribe the exact #'s...possible reason for this were not discussed, nor was he asked...
Next abstract presented by Dr. J.A. Bonner, chief PI for this international trial.
Phase 111 study of high dose radiation with or without cetuximab in the treatment of locoregionally advanced squamous cell cancer of the head and neck(SCCHN). Authors ranged from the University of Alabama, Vall D'Hebron Hospital in Barcelona, Spain, U's of Wisconsin, Virginia, Radiation Oncology Ctr in Sacramento, CA; Johannesburg Hospital, South Africa, U of Colorado, and U of Texas M.D. Anderson Cancer Center in Houston, TX
From the abstract: Methods: Patients with locoregionally advanced SCCHN(squamous cell cancer of the head and neck) with one of three high dose radiation treatment schedules, single daily fractions(26%), twice daily fractions(18%), or concomitant boost fractionation(56%) to a dose of 70Gy, at the discretion of the treating physician. Patients were stratified by the type of radiation and and prospectively randomized 1:1 to receive or not to receive cetuximab. Cetuximab was given IV at 400mg/m2 one week prior to the start of radiation and for seven weekly doses of 250mg/m2 during radiation.
Endpoints included local regional control, time to progression, and survival.Results: 424 patients were entered and randomized, meeting target accrual of 416. Median age was 57; 80% male; 83% white; median Karnofsky score 90; the two cohorts were well balanced. Patients on the C arm were more likely to experience fever/chills(38%/16%) and nausea vomiting(53%/41%) but not fatigue/malaise(56%/50%) or stomatitis(91%/93%) Rash was common in both groups, but more common in the C group (97%/90%); grade 3 rash(34%/18%). Six patients(3%) on the C arm experienced grade 3 or 4 allergic reactions.
Presentation made by J.A. Bonner the principle investigator of the trial.
I'll try to report everything he said, but the slides were gone through too rapidly for me to write down many figures...those with the digital cameras photographing the slides definitely with an edge...
All patients were chemo/radiation naive...consisted of stage 1-4 disease, some patients had surgical dissection, salvage surgery, secondary radiation and chemotherapy during study.
Overall survival was 54mos for C arm and 28 months for Radiation arm.P value?....slides too fast, but definitely under 0.05. Locoregional control 57% for C arm, 44% Radiation arm. P value=O.02(this I'm sure of)...
Discussion of results by Dr. Bonner:
-We restricted to locoregional control as one of the endpoints because these patients develop other lesions/cancers which would make it difficult to make accurate conclusions.
-208 patients evaluated for presentation.
-choice of radiation was left to the discretion of the clinical investigator
-all data, films reviewed by priniciple institutional investigators...but not allowed to review own hospital's data
-69% of patients with T3-T4 lesions...slides going so fast, I was unable to see distribution in both arms.
-No slides of distribution of patients that received surgical dissection, salvage surgery, or secondary radiation and chemo during study.
Dr. Bonner: "We are very pleased with this study that shows Erbitux does give survival advantage for this population. We are very pleased that Erbitux did not increase the incidence of stomatitis.
Q&A...
1)"Congratulations on your successful efforts...in your subgroup analysis, did you happen to see improvements in distant control." reply: No. Subgroup analysis not done.
2)by a practicing oncologist..."Is it reasonable to add Erbitux to the standard RT/Chemo regimen." reply: um, that is up to your discretion, we've not done large trials to draw a benefit conclusion"....same doctor 2nd question..."Do you think Erbitux will act synergistically with chemo to further improve survival?"...reply: I don't know. Studies ongoing.
3)Me..."I applaud your hard work with this molecule, a couple of questions. First,I did not see slides showing distribution of patients by stage and radiation dose in both arms. Can you clarify this for me?" Answer: First of all, most patients were stage 3 or 4, the type of radiation was left to the discretion of the investigator. The majority chose concomitant boost fractionation." Thanks, second question...Dr. Pinto interrupted, calling on another person who also asked about subgroup details...
My second and 3rd questions were going to be: Rationale for not using IRB since it is common practice for a late stage trial especially in light of Erbitux being a novel agent...Since subgroup distribution data unavailable, and the boost fractionation method used most, is there historical data to demonstrate it's possible impact on the results?
4)by another oncologist...how did patients with surgical intervention do?..."No subset analysis."
Dr. Langer provided a brief critique of the trial..."great results, but confirmatory trials needed to draw definitive conclusions, subgroup analysis and subsequent trials needed.
Next trial...P2 trial using erbitux+cisplatinum in platinum refractory patients...75 patients, standard C dosage and weekly erbitux by IV...
Overall response rate=13%
Disease control=47%
2.1 months median time to progression
5.5 month median survival
CR=0, PR=0, SD(stable)yes(slide too fast to record), PD(progressive disease) yes(slide to fast to record) wish I had my digital camera with me at this point!
Showed slide of different drugs(ie. Iressa which showed 3.4 month median survival)
Recommendations to use for second line therapy in SCCHN.
A few questions about drug interactions...none...
The next presentation for cisplat/5FU compared to taxotere +5FU announced...
Audience gets up to leave along with Bonner. Cameras readying for trip back home.... |
