M. D. ANDERSON CANCER CENTER'S PANCREATIC TUMOR STUDY GROUP AT THE ASCO 35TH ANNUAL MEETING May 15-18, 1999 Atlanta, GA
ASCO 1999 AWARD RECIPIENTS FROM M. D. ANDERSON'S PANCREATIC TUMOR STUDY GROUP
Dr. Tara M. Breslin (Surgical Fellow/ Laboratory Scientist) will be receiving a Young Investigator Award, sponsored by Ortho Biotech-Janssen Research
Dr. Jason Fleming (Surgical Fellow) will be receiving a 1999 ASCO Merit Award.
M. D. ANDERSON PANCREATIC TUMOR STUDY GROUP ABSTRACTS/PRESENTATIONS
General
Poster Session: "Gastrointestinal Cancer I"
Date/Time: Saturday, May 15, 1999; 1 PM - 5 PM
Location: Hall C, East Wing
Abstract #939
Peter WT Pisters, et al
"Comparative Toxicities of Preoperative Paclitaxel vs 5-Fluorouracil-Based Rapid Fractionation Chemoradiation for Resectable Pancreatic Adenocarcinoma (Poster Bd #E4)
We have utilized rapid-fractionation chemoradiation in the preoperative treatment of 72 patients with resectable pancreatic adenocarcinoma in 2 sequential protocols that employed either 5-fluorouracil (5-FU, n=35) or paclitaxel (n=37) as radiosensitizers. Patients with localized, resectable pancreatic adenocarcinoma were treated with 30 Gy radiation (3 Gy/Fx, M-F over 2 weeks) and concomitant continuous infusion 5-FU (300 mg/m2, M-F) or bolus paclitaxel (60 mg/m2, days 1,8,15). We compared the acute toxicities and degrees of pathologic response with these 2 regimens. Results: Among 35 patients treated with 5-FU/30 Gy, 3 (9%) experienced grade 3 gastrointestinal toxicity. No other grade 3 toxicities were noted; 1 patient required hospitalization for occlusion of an endobiliary stent. Of the 37 patients treated with paclitaxel/30 Gy, 18 (49%) experienced grade 3 toxicities: gastrointestinal toxicities (n=5), granulocytopenia (n=3), leukopenia (n=3), anorexia (n=3), and general toxicities (fatigue, depression, dehydration, and allergic reaction in 1 patient each). Hospitalization for dehydration secondary to grade 3 nausea and vomiting was required in 4 patients (11%) treated with paclitaxel/30 Gy. No patients treated with either regimen experienced grade 4 treatment-related toxicity, and there were no treatment-related deaths. Pathologic response to preoperative chemoradiation was evaluated with an objective grading system (Evans et al. Arch Surg 127:1335, 1992) in the 39 patients who underwent subsequent pancreaticoduodenectomy. No complete pathologic responses were observed. The distribution of grade I (<10% tumor destruction), grade IIA (10-50% tumor destruction), and grade IIB (51-90% tumor destruction) pathologic responses in the 2 treatment groups were similar: 11 grade I, 5 grade IIA, and 4 grade IIB responses in the 5-FU/30Gy group and 8 grade I, 7 grade IIA, and 4 grade IIB responses in the paclitaxel/30 Gy group. Conclusion: Paclitaxel-based rapid-fractionation preoperative chemoradiation is associated with a broader, more significant overall toxicity profile than is similar treatment with 5-FU. The distribution of pathologic responses is similar, suggesting no immediate advantage to paclitaxel-based preoperative treatment. Long-term follow-up of patients in both protocols continues.
Poster
Discussion Session: "Gastrointestinal Cancers: Esophageal, Gastric,
and Pancreatic Cancer"
Date/Time: Tuesday, May 18, 1999; 8 AM - 12 PM
Discussion Location/Time: 205E; 11 AM - 12
Discussion
Co-Chair from M D Anderson will be Jaffer A Ajani, MD)
Abstract #1048
M. Tempero, et al
"Randomized Phase II Trial of Dose Intense Gemcitabine By Standard Infusion vs. Fixed Dose Rate in Metastatic Pancreatic Adenocarcinoma." (Poster Bd #15)
Gemcitabine (GEM) undergoes intracellular phosphorylation to form the active di- and triphosphates, the rates of formation of which are dose rate dependent. In order to determine if altering dose rate translates into therapeutic benefit, we conducted a randomized phase II trial of 2 dose intense regimens of GEM in patients with metastatic pancreatic adenocarcinoma. All pts had histologic confirmation of disease, no prior treatment, and performance status ECOG 0-2. Pts were randomized to receive GEM (2200 mg/M2) over standard 30 min infusion (Arm A) or GEM (1500 mg/M2) at a rate of 10 mg/M2/minute (Arm B) weekly x 3 every 4 weeks. Pharmacokinetic studies were performed on selected pts. Ninety-three pts have been accrued and the trial is closed. Eleven pts are inelligible (9 without metastases, 2 other diagnoses) and 15 pts are too early to evaluate or data are incomplete. Analysis has been completed on 67 pts.
|
ARM
|
N
|
OBJ
RESP
|
TIME
TO PROG
|
MED
SURV
|
1
YR SURV**
|
|
A
|
37
|
2.7%
|
1.9
MOS.
|
4.7
MOS.
|
0%
|
|
B
|
30
|
16.6%*
|
2.2
MOS.
|
6.1
MOS.
|
23%
|
*Includes 2 pts with complete remission **Based on actuarial analysis; 12 (Arm A) and 7 (Arm B) pts are still living.
In addition, the median GEM triphosphate in mononuclear cells at the end of each infusion was significantly different: Arm A, 114 microM, n = 7; Arm B, 336 microM, n = 10 (p = 0.003). This data does not support dose intensification with GEM over a standard 30 min infusion. However, early analysis suggests that a fixed dose rate infusion results in more objective responses, longer median survival, and higher 1 year survival than previously reported. This infusion schedule deserves further study and should be tested with potentially synergistic drug combinations such as GEM plus cisplatin.