Thomas W. Griffin

Initial clinical trials of the subrenal capsule assay as a predictor of tumor response to chemotherapy

Retrospective and prospective clinical trials were performed to determine the usefulness of the 6‐day subrenal capsule (SRC) assay for the prediction of response to chemotherapy. Evaluable assays were obtained in 86% of 1000 consecutive specimens obtained from a variety of solid malignancies. Analysis of chemotherapeutic sensitivity in this assay gave reproducible and consistent results. The overall predictive accuracy of the assay in 62 retrospective clinical trials in 55 patients was 85%. Of 37 evaluable patients with chemotherapy refractory cancers treated in a prospective trial with single agent chemotherapy as determined by the assay, 14 (38%) responded. Greater degrees of tumor regression in the assay were associated with a higher probability of clinical response. The SRC assay shows potential value as a rapid predictive test for chemotherapeutic selection on an individual patient basis. However, additional prospective clinical trials are necessary to document its ultimate utility. Cancer 52:2185‐2192, 1983.

Use of indium-111-labeled OC-125 monoclonal antibody in the detection of ovarian cancer

Abstract This is a preliminary study to evaluate the utility of using the monoclonal antibody (CO-125) labeled with indium-111 to image recurrences of ovarian cancer. This technique has been investigated in 23 patients with ovarian cancer and the results have been compared with blood OC-125 levels, CT scans, and findings at second-look surgery. Following infusion of 1 mg of F(ab′) 2 fragments (1–2 mCi 111 In), quantitative SPECT and planar imaging was obtained daily for 72 hr along with analysis of serum. The nuclear medicine scans of the tumor site recurrences were technically excellent. When compared to second-look laparotomy, there were 2 true negatives, 2 false positives, 14 true positives, and 2 false negatives by nuclear imaging. CT scans correlated less well with surgery, but serum OC-125 levels correlate more closely with nuclear scans and second-look surgery. Those with multiple small metastatic implants showed a pattern of diffuse uptake which increased with time, whereas those with nodal or larger recurrences showed a more focal uptake. The combination of favorable biodistribution and positive images, especially in patients with normal antigen levels and negative CT scans, suggests a role for OC-125 monoclonal antibody imaging in their clinical management. However, further investigation is needed to determine whether nuclear scans can replace second-look surgery. If it can show that enough 111 In-labeled antibody accumulates in the tumor site to justify radioimmunotherapy, then 90 Y (a pure beta emitter) could be exchanged for 111 In. This is potentially a method of radioimmunotherapy for recurrent ovarian carcinoma.

Comparison of abdominopelvic computed tomography results and findings at second-look laparotomy in ovarian carcinoma patients

In 35 women with epithelial carcinoma of the ovary, the results of restaging laparotomy were compared with the preoperative abdominopelvic computed tomography (CT) findings to evaluate the accuracy of CT for determining tumor status. In the 36 studies performed, enhanced CT scans at 10‐mm to 15‐mm intervals had a sensitivity of 84% and a specificity of 88%; in addition, there was 86% agreement between the CT and surgical findings. These results suggest that although CT is not accurate enough to completely replace the restaging laparotomy, its high accuracy in determining residual disease after treatment is helpful for patient management.

Responsiveness of gynecologic tumors to chemotherapeutic agents in the 6-day subrenal capsule assay

Abstract Various gynecologic malignancies have been tested in the 6-day subrenal capsule assay, which is an in vivo test of human tumor responsiveness to drug therapy. Fresh surgical explants of ovarian, endometrial, and cervical tumors were implanted as 1-mm 3 fragments under the renal capsule of normal mice and tested against a spectrum of clinically active agents. Regardless of the site of origin, human tumors showed variations in growth rate when implanted under the renal capsule that appeared to reflect both the growth potential characteristic of each tumor as well as the heterogeneity of the cell populations comprising each tumor. An average of 60% of tumors showed positive growth and 11% demonstrated no measurable change in size. The response rates of 18 ovarian, 28 endometrial, and 20 cervical carcinomas to clinically active chemotherapeutic agents were determined. A range of responses, in terms of drugs indicated to be active and of the degree of responsiveness to active agents, was obtained with each histologic type. Response rates varied from 6% to tamoxifen in cervical carcinomas to 80% to 5-fluorouracil in ovarian carcinomas. The results of this study support the variability in chemotherapy responsiveness observed clinically with gynecologic tumors and suggest the feasibility of using the subrenal capsule assay as a predictive test.

Synchronous occurrence of glioblastoma multiforme in a husband and wife

Glioblastomas developed within two years of each other in an otherwise unrelated married couple in their fifties. There was a daughter who died of Hodgkins disease but no other unusual incidence of cancer in either siblings, parents or other children. No clear etiology of risk factors for brain tumor were identified. The development of such conjugal tumors, although apparently rare, raises important etiologic questions.

High-dose, short-duration cisplatin/doxorubicin combination chemotherapy for advanced ovarian epithelial cancer

Sixty‐one patients with epithelial ovarian cancer were treated with intensive high‐dose, short‐course chemotherapy that consisted of cisplatin (120 mg/m2) and doxorubicin (70 mg/m2) every 3 weeks for four cycles. Patients in complete clinical remission were offered second‐look laparotomy (SLL). Patients with minimal or no residual disease at SLL were randomized to either cyclophosphamide (1000 mg/m2 every 21 days for six cycles) or whole‐abdominal radiation therapy. All patients completed therapy with a median leukocyte nadir 1.3/μl and platelet nadir of 90/μl. Forty‐five patients (74%) had a complete clinical response. Results of twenty‐two of 36 second‐look procedures (64%) showed no evidence of disease (NED). After SLL, 19 patients received six courses of cyclophosphamide and 16 patients received whole‐abdominal radiation. Nine patient who refused SLL and one patient with negative SLL findings refused additional treatment. The median survival time for all patients was 51.3 months. High‐dose intensive chemotherapy regimens have high response rates, but survival needs to be compared with traditional low‐dose regimens. Although high‐dose cisplatin and doxorubicin were myelosuppressive, the resulting complications were manageable. There was no significant difference between the mean survival times of patients receiving Cytoxan, abdominal radiation, or no treatment as second‐line therapy.

Immunoscintigraphy Using F(Ab—)2 Fragments

The purpose of the study was to evaluate in patients the pharmacokinetics, biodistribution, and tumor localization potential of the Indium-111 labeled F(ab’) 2 fragments of the antibody 19-9 coupled with DTPA using a method we have developed (1). These studies were carried out in 13 patients who either had known sites of tumor or in whom recurrence of tumor was suspected.