Michael G. Hanna

Adjuvant Active Specific Immunotherapy for Stage II and III Colon Cancer With an Autologous Tumor Cell Vaccine: Eastern Cooperative Oncology Group Study E5283

PURPOSE A randomized phase III clinical trial of adjuvant active specific immunotherapy (ASI) with an autologous tumor cell-bacillus Calmette-Guérin (BCG) vaccine was conducted to determine whether surgical resection plus ASI was more beneficial than resection alone in stage II and III colon cancer patients. PATIENTS AND METHODS Patients (n = 412) with colon cancer (297 with stage II disease, 115 with stage III disease) were randomly allocated to an observation arm or to a treatment arm in which they received three weekly intradermal vaccine injections of 10(7) irradiated autologous tumor cells beginning approximately 4 weeks after surgery. The first two weekly injections also contained 10(7) BCG organisms. Patients were observed for determination of time to recurrence and disease-free and overall survival. RESULTS This was a negative study in that after a 7.6-year median follow-up period, there were no statistically significant differences in clinical outcomes between the treatment arms. However, there were disease-free survival (P =.078) and overall survival (P =.12) trends in favor of ASI when treatment compliance was evaluated, ie, patients who received the intended treatment had a delayed cutaneous hypersensitivity (DCH) response to the third vaccination (induration >/=5 mm). Also, the magnitude of the DCH response correlated with improved prognosis. The 5-year survival proportion was 84.6% for those with indurations greater than 10 mm, compared with 45.0% for those with indurations less than 5 mm. CONCLUSIONS When all randomized patients were evaluated, no significant clinical benefit was seen with ASI in surgically resected colon cancer patients with stage II or III colon cancer. However, there was an indication that treatment compliance with effective immunization results in disease-free and overall survival benefits.

Radioimmunoscintigraphy of recurrent, metastatic, or occult colorectal cancer with technetium Tc 99m 88BV59H21-2V67-66 (HumaSPECT®-Tc), a totally Human monoclonal antibody-patient management benefit from a phase III multicenter study

PURPOSE: The study contained herein was undertaken to evaluate the accuracy of radiolabeled human monoclonal antibody, 88BV59H21-2V67-66 (88BV59 or HumaSPECT®-Tc), in predicting disease resectability in presurgical subjects with recurrent, metastatic, or occult colorectal carcinoma. METHODS: A total of 219 patients with disease visualized on computed tomographic scan (recurrent or metastatic disease) or with negative or equivocal computed tomographic scan and rising carcinoembryonic antigen serum levels (occult group) received technetium Tc 99m-labeled 88BV59 intravenously. Planar and single photon emission computed tomographic images were obtained 14 to 20 hours postinfusion, before surgery. The ability of computed tomographic and HumaSPECT®-Tc imaging to define the extent of disease and to predict resectability was evaluated based on surgical and histopathologic results. RESULTS: In patients with recurrent or metastatic disease (170 evaluable patients), the accuracy of predicting non-resectability of disease was significantly greater (P<0.001) for HumaSPECT®-Tc than for computed tomography (60vs. 29 percent). Computed tomography understaged 41 percent of patients believed to have resectable disease compared with 27 percent for HumaSPECT®-Tc (P<0.001). In occult disease patients (29 computed tomographic and 28 HumaSPECT®-Tc evaluable patients), the overall accuracy of predicting resectability/nonresectability was 68 percent for HumaSPECT®-Tc compared with 24 percent for computed tomography. Administration of HumaSPECT®-Tc had no effect on monoclonal antibody-basedin vitro diagnostic assays. Only a single patient demonstrated an anti-antibody response (90 ng/ml) at nine weeks postinfusion. CONCLUSION: HumaSPECT®-Tc was more accurate than computed tomography in determining disease resectability in patients with metastatic, recurrent, or occult cancer. The addition of HumaSPECT®-Tc imaging can play a significant role in patient management decisions.