Chemoradiotherapy of esophageal carcinoma.

BACKGROUND: Chemoradiotherapy has demonstrated efficacy in esophageal cancer but rarely is curative. To improve local control and decrease metastases, a 7-month regimen was used with standard-dose radiotherapy (RT), cisplatin (DDP), and continuous infusion (CI) 5-fluorouracil (5-FU) in patients with locoregional squamous/adenocarcinoma of the esophagus. METHODS: Initial treatment consisted of RT to the esophagus (4000-5000 cGy) for 5-6 weeks, CI 5-FU (300 mg/m2/day) concurrent with RT, and DDP (25 mg/m2/day x 3) for Days 1-3 and 21-23. Two monthly cycles of DDP (75 mg/m2 Day 1) and 5-FU (300 mg/m2 x 21 days) followed. Patients were restaged with endoscopy and computed tomography scan. Patients without evidence of residual disease received three more cycles of chemotherapy (CT); those with persistent tumor underwent esophagectomy or additional CT/RT, and those with disease progression were offered alternative CT. RESULTS: From December 1987 to September 1991, 18 men and 8 women, including 2 with adenocarcinoma, were eligible for inclusion in the study. All were evaluable for toxicity and response. The median age was 61.5 years (range, 50-80 years), the median pretreatment weight loss was 9 lbs, and the median serum albumin level was 4.3 mg%. Therapy was toxic; 19 patients were hospitalized for treatment-related esophagitis, thrombosis, or infection. Grade III and IV leucopenia were seen in 12 patients and 1 patient, respectively. One patient had Grade IV thrombocytopenia. Of 26 patients, 17 (65%) had no tumor on restaging. Five patients had recurrences in the esophagus (1), liver (3), and lung (2). Three patients had second neoplasms. The median survival was 24 months. CONCLUSION: This treatment regimen provides high frequency of local tumor resolution, but with significant toxicity.

Continuous infusion ABDIC therapy for relapsed or refractory Hodgkin's disease.

BACKGROUND: Patients whose Hodgkin's disease is refractory to standard combination chemotherapy usually have a poor prognosis. These patients are generally considered for bone marrow transplantation if the disease is still sensitive to chemotherapy. METHODS: Between May 1988 and January 1992, 19 patients with refractory or relapsed Hodgkin's disease were treated with a regimen of doxorubicin, bleomycin, dacarbazine, lomustine, and prednisone (ABDIC). The ABDIC regimen as modified for continuous infusion by Hagemeister consisted of doxorubicin 25 mg/m2 by continuous infusion daily for 2 days, dacarbazine 200 mg/m2 by continuous infusion daily for 5 days, bleomycin 5 U/m2 intravenously on days 1 and 5, CCNU 40 mg/m2 on day 1, and prednisone 40 mg/m2 daily on days 1-5. Treatment was repeated every 28 days. RESULTS: At the time of treatment, mean age was 30.5 years (range 19-70), and time to ABDIC from initial diagnosis was 5.6 years (range 1-14). The mean number of prior chemotherapy regimens was 2.7 (range 1-5), and three of the patients had had autologous bone marrow transplantation before ABDIC: All patients had earlier received either mechlorethamine, vincristine, procarbazine, and prednisone or a regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine, and 16 had received both. The mean number of ABDIC cycles was 3.9 (range 2-12). Total response rate was 63%, with 10 patients having partial response and 2 having complete response of 12 and 27 months' duration. Seven patients subsequently underwent bone marrow transplantation; two of these are free of disease at 35 and 41 months. The treatment was well tolerated; major toxicities were nausea and bone marrow suppression. CONCLUSION: ABDIC is an active and well tolerated therapy in patients with relapsed or refractory Hodgkin's disease, including those previously treated with ABVD. More importantly, perhaps, ABDIC as cytoreductive therapy followed by bone marrow transplantation offers the possibility of long term disease free survival in this heavily pretreated patient population.

Tumor-associated angiogenesis in prostate cancer.

All solid tumors require the induction of new blood vessels to grow. To begin to study this phenomenon in prostate cancer, we investigated the intensity of tumor associated angiogenesis in prostate non malignant and malignant tissue. Angiogenesis was measured by quantitating microvessels in a total of 67 patients: 23 non malignant biopsy specimens, and 34 malignant specimens from patients who had undergone prostatectomy. Angiogenic activity in prostatic cancer (prostatectomy) tissue (utilizing Factor VIII staining) was then correlated with pathological staging (Whitmore-Jewitt). Overall there appeared to be a trend of increasing microvessel count (MVC) from benign through the advancing stages of prostate cancer. Based on mean microvessel counts we were able to distinguish stage D from all other pathological stages (p = 0.004 between stages C and D). There was, however, no statistically significant difference between stage B and C. We conclude that tumor associated angiogenesis in prostate cancer may have both clinical and pathological significance in prostate cancer.

Nuclear matrix proteins in normal and breast cancer cells.

The progression from normal breast epithelium to a malignant phenotype may depend on changes in genetic events as well as failure of host mechanisms. Intermediate biomarkers are needed to more effectively identify malignant progression as well as to develop the potential for more specific treatments and prevention strategies. The nuclear matrix is the RNA-protein network which forms the skeleton of the nucleus and participates in DNA organization as well as multiple cellular functions. Nuclear matrix proteins have been demonstrated to be tissue and cell type specific as well as to reflect the state of cell differentiation and/or transformation. We prepared nuclear matrices from normal and cancer breast tissue from 10 patients with infiltrating ductal carcinoma of the breast as well as the MCF-10 mortal, immortal, and transfected breast cell lines. Nuclear matrices derived from normal human breast tissue and tumor tissue share common nuclear matrix proteins as well as demonstrate specific changes which appear to occur with the acquisition of the cancer phenotype. The MCF-10 cell lines demonstrate a phenotype that is intermediate between the normal and cancer tissue. These data suggest that the nuclear matrix may be an important biomarker in the pathogenesis of breast cancer.

Angiodysplasia in transposed colon.

A 40-year-old man with a history of colonic transposition for lye stricture at 10 years of age presented with upper gastrointestinal tract bleeding due to angiodysplasia in a transposed right colon.