Norman C. Estes

Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer.

BACKGROUND We performed a multi-institutional randomized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer. METHODS Preoperative chemotherapy for patients randomly assigned to the chemotherapy group included three cycles of cisplatin and fluorouracil. Surgery was performed two to four weeks after the completion of the third cycle; patients also received two additional cycles of chemotherapy after the operation. Patients randomly assigned to the immediate-surgery group underwent the same surgical procedure. The main end point was overall survival. RESULTS Of the 440 eligible patients with adequate data , 213 were assigned to receive preoperative chemotherapy and 227 to undergo immediate surgery. After a median possible study time of 55.4 months, there were no significant differences between the two groups in median survival: 14.9 months for the patients who received preoperative chemotherapy and 16.1 months for those who underwent immediate surgery (P=0.53). At one year, the survival rate was 59 percent for those who received chemotherapy and 60 percent for those who had surgery alone; at two years, survival was 35 percent and 37 percent, respectively. The toxic effects of chemotherapy were tolerable, and the addition of chemotherapy did not appear to increase the morbidity or mortality associated with surgery. There were no differences in survival between patients with squamous-cell carcinoma and those with adenocarcinoma. Weight loss was a significant predictor of poor outcome (P=0.03). With the addition of chemotherapy, there was no change in the rate of recurrence at locoregional or distant sites. CONCLUSIONS Preoperative chemotherapy with a combination of cisplatin and fluorouracil did not improve overall survival among patients with epidermoid cancer or adenocarcinoma of the esophagus.

Phase III Trial of Fluorouracil-Based Chemotherapy Regimens Plus Radiotherapy in Postoperative Adjuvant Rectal Cancer: GI INT 0144

PURPOSE Adjuvant chemoradiotherapy after or before resection of high-risk rectal cancer improves overall survival (OS) and pelvic control. We studied three postoperative fluorouracil (FU) radiochemotherapy regimens. PATIENTS AND METHODS After resection of T3-4, N0, M0 or T1-4, N1, 2M0 rectal adenocarcinoma, 1,917 patients were randomly assigned to arm 1, with bolus FU in two 5-day cycles every 28 days before and after radiotherapy (XRT) plus FU via protracted venous infusion (PVI) 225 mg/m2/d during XRT; arm 2 (PVI-only arm), with PVI 42 days before and 56 days after XRT + PVI; or arm 3 (bolus-only arm), with bolus FU + leucovorin (LV) in two 5-day cycles before and after XRT, plus bolus FU + LV (levamisole was administered each cycle before and after XRT). Patients were stratified by operation type, T and N stage, and time from surgery. RESULTS Median follow-up was 5.7 years. Lethal toxicity was less than 1%, with grade 3 to 4 hematologic toxicity in 49% to 55% of the bolus arms versus 4% in the PVI arm. No disease-free survival (DFS) or OS difference was detected (3-year DFS, 67% to 69% and 3-year OS, 81% to 83% in all arms). Locoregional failure (LRF) at first relapse was 8% in arm 1, 4.6% in arm 2, and 7% in arm 3. LRF in T1-2, N1-2, and T3, N0-2 primaries who received low anterior resection (those most suitable for primary resection) was 5% in arm 1, 3% in arm 2, and 5% in arm 3. CONCLUSION All arms provide similar relapse-free survival and OS, with different toxicity profiles and central catheter requirements. LRF with postoperative therapy is low, justifying initial resection for T1-2, N0-2 and T3, and N0-2 anterior resection candidates.

Adjuvant chemotherapy with 5-FU, adriamycin, and mitomycin-C (FAM) versus surgery alone for patients with locally advanced gastric adenocarcinoma: A southwest oncology group study

AbstractPurpose: To evaluate FAM [5-FU (5-fluorouracil), doxorubicin, mitomycin C] chemotherapy as adjuvant therapy for patients with resected TNM stage I, II, or III gastric carcinoma. Patients and Methods: One hundred ninety-three eligible patients were accrued from 1978 to 1991 in a phase III trial comparing six cycles (1 year) of postoperative FAM chemotherapy with observation only. Results: The median follow-up on this study was 9.5 years. For all patients, no differences (log-rank analysis) in disease-free survival (p=0.45) and overall survival (p=0.57) between FAM therapy (93 cases) and surgery (100 cases) were observed. Quality of surgical resection affected survival irrespective of FAM use. Cases with curative resection, defined in a retrospective review of pathology and surgical reports as cases having no evidence of residual disease in the abdomen and tumor-free margins >1 cm, had superior survival compared to cases not meeting these requirements (p<0.001). FAM was well tolerated with 6% (five of 90) of cases demonstrating grade IV hematologic toxicity. There were two drug-related fatalities (one cardiomyopathy, one hematolytic uremic syndrome). Conclusion: FAM is not effective adjuvant therapy for TNM stage I, II, and III patients with resected gastric cancer. Future adjuvant studies must emphasize prospective surgical quality control to assure enrollment of appropriately staged and resected cases and wide participation to assure adequate case accrual over a reasonable period.

Chylous ascites following abdominal aortic aneurysmectomy. Management with total parenteral hyperalimentation.

Chylous ascites may follow operative injury to retroperitoneal lymphatics. When possible, early reoperation has been advised. This report describes a patient with chylous ascites following emergency abdominal aortic aneurysmectomy. Because the patient was not a candidate for reoperation, total parenteral hyperalimentation was employed in management. This approach resulted in a successful outcome.

Adjuvant continuous infusion 5-FU, whole-abdominal radiation, and tumor bed boost in high-risk stage III colon carcinoma: A southwest oncology group pilot study

PURPOSE Results of a combined modality adjuvant pilot program of low-dose continuous-infusion 5-fluorouracil, whole-abdominal radiation, and tumor bed boost in patients with colon cancer with involved nodes and serosal involvement are presented. METHODS AND MATERIALS Forty-one eligible patients with completely resected T3N1-2M0 colon cancer (modified Astler-Coller C2) were treated with 5-fluorouracil (5-FU) at a dose of 200 mg/m2/day by continuous infusion and 30 Gy of concomitant whole-abdominal radiation in 1 Gy fractions. An additional 16 Gy boost to the tumor bed was administered in 1.6 Gy fractions. After completion of combined modality treatment and a 21-day rest period, patients received 4 days of 5-FU at a dose of 1000 mg/m2 by continuous infusion every 28 days for nine cycles. RESULTS Five-year disease-free and overall survival estimates were 58 and 67%, respectively, for all T3N1-2 patients. Five-year disease-free and overall survival estimates for the 19 patients with four or fewer nodes were both 61%. Five-year disease-free survival and overall survival estimates for the 20 patients with more than four involved nodes were 55% and 74%, respectively (the exact number of involved nodes were unknown for two patients). Disease-free and overall survival estimates for patients treated with 5-FU and radiation compare favorably to the 5-FU plus levamisole arm of the intergroup adjuvant colon study (Int 0035/SWOG 8591) in patients with more than four positive nodes where the 5-year disease-free and overall survival estimates were 35% and 39%, respectively. Disease-free and overall survival estimates for patients with four or fewer nodes in the 5-FU plus levamisole arm of the intergroup study were 64 and 68%, which is not markedly different from results obtained with radiation and 5-FU in the current study. There were no treatment-related fatalities. Seventeen percent of patients had severe and 7% had life-threatening toxicity of any kind. One patient had an acute partial bowel obstruction and two patients had chronic low grade enteritis. CONCLUSION Continuous infusion 5-FU and whole-abdominal radiation with tumor bed boost should be further investigated in a larger trial of T3N1-2 colon cancer.

Intraarterial chemotherapy and hyperthermia for pain control in patients with recurrent rectal cancer

For the majority of patients with unresectable recurrence of rectal cancer, persistent pain is the most distressing problem. This brief study describes a method to control pain in 10 patients with unresectable rectal cancer confined to the pelvis after standard therapy failed. All of the patients had percutaneous placement of infusion catheters in both internal iliac arteries. A continuous intraarterial infusion of 800 mg/m2 of 5-fluorouracil per day was given for 7 days and 10 mg/m2 of mitomycin C was administered as a bolus injection on the seventh day only. Four patients also received whole body hyperthermia by way of a Erbotherm 434 mHz microwave generator on the second and fifth days of infusion. Relief of pain occurred in three of the six patients who received intraarterial chemotherapy only. All four patients who also received hyperthermia achieved prolonged pain relief when it was added. We have concluded that intraarterial chemotherapy may be beneficial in patients with uncontrolled pelvic pain due to recurrent rectal cancer. The addition of hyperthermia may augment the benefit.

Serum antibody in patients with mammary disease

Antibody to a breast cancer antigen was detected by immunodiffusion or complement fixation in at least one serum sample in 46% of 84 patients with a diagnosis of carcinoma, 34% of 96 patients with fibrocystic disease, and 25% of 44 patients with fibroadenoma. A single serum sample obtained from screenees of the Detection Center for Breast Diseases was tested by immunodiffusion only, and antibody was found in 3 of 206 screenees (1.5%). Eleven of 13 patients with breast cancer metastatic to lymph nodes and no detectable serum antibody either had recurrence or were dead within 12 months of mastectomy. Fifteen of 18 patients with breast cancer metastatic to lymph nodes and with detectable serum antibody were alive and free of disease for up to 24 months. Data to date indicate that serum antibody in the patient with breast disease cannot be used at this time as an “early detection test.” As a seroprognostic factor in patients with breast cancer metastatic to lymph nodes, the finding of antibody has great promise.

Role of Herniography in the Diagnosis of Occult Hernias

Twenty-two patients with groin or incisional pain and normal physical examinations underwent herniography. Eight patients were found to have 11 unsuspected hernias. Seven were direct, two indirect, and two incisional. Six of nine groin hernias were recurrent. Exploration confirmed the herniographic findings in all patients. Follow-up evaluation of patients undergoing herniorrhaphy revealed resolution of symptoms. Ten of the 14 patients with normal herniograms were asymptomatic 3 months after herniography. In these 22 patients, herniography resulted in a savings of

Mastodynia due to fibrocystic disease of the breast controlled with thyroid hormone

31,000. We conclude that herniography is cost-effective and useful in patients with abdominal wall pain of obscure etiology.

Serum Antibody in Patients with Breast Disease: Correlation with Histopathology

Nineteen patients were evaluated for breast pain and nodularity associated with fibrocystic disease. Rapid pain relief occurred in 73 of patients, with total relief in 47 percent after daily treatment with 0.1 mg of levothyroxine. Softening of breast tissue and decreased nodularity occurred within 3 months in many patients. Three patients had elevated levels of serum prolactin before treatment, with dramatic pain relief and normalization of prolactin levels after treatment. Further trials of levothyroxine in patients with mastodynia due to fibrocystic disease appear justified.