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Biomedical subjects

L Leichman

Publications and source records attributed to L Leichman.

50 records · Page 3Linked to original sources
PubMed1987

Combined therapies for squamous-cell carcinoma of the esophagus, a Southwest Oncology Group Study (SWOG-8037).

Conservative treatment of esophageal cancer with radiation therapy has afforded few long-term survivors. In order to improve outcome, patients with locoregional disease were treated using a combined modality approach. Patients were treated with chemotherapy consisting of a 96-hour continuous infusion of 5-fluorouracil (5-FU), 1,000 mg/m2/d, days 1 to 4 and days 29 to 32; cisplatin 75 mg/m2, day 1 and 29; and radiation 3,000 rad, days 1 to 19. In the absence of progressive disease, patients underwent esophagectomy. One hundred twenty-eight patients were registered of whom 113 were eligible and 106 were evaluable. Toxicity included gastrointestinal (GI) symptoms, mucositis, and myelosuppression. One hundred two patients completed chemoradiotherapy. Following its completion, 11 patients refused surgery, six were considered poor surgical risks, and 14 had progressive disease. Of the remaining 71 patients, 16 had unresectable disease, 13 had residual disease which was incompletely resected, 24 had disease which could be completely resected, and 18 were without disease on pathologic examination. The overall operability rate was 63% and the overall resectability rate, 49%. Surgical mortality was 11%. Eighty-nine of 113 eligible patients have died, with a median survival of 12 months and a 2-year survival of 28%. The median postsurgical survival for all 71 patients was 14 months and was 32 months for those patients attaining complete remission (CR). Combined modality therapy remains an investigational approach. Attempts should be directed at increasing response rate to initial therapy. A randomized comparison between combined modality treatment and radiation therapy is necessary to definitively determine the usefulness of this more aggressive approach.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

High-dose mitomycin-C with autologous bone marrow transplantation in patients with refractory malignancies. Influence of dose schedule on pharmacokinetics and nonhematopoietic toxicities.

Thirteen courses of high-dose mitomycin-C with autologous bone marrow transplantation (ABMT) were administered to 12 patients. Four dose schedules were evaluated: A) 60 mg/M2 X 1, 60-min infusion; B) 30 mg/M2/day X 2, 15-min infusion; C) 30 mg/M2/day X 2, 60-min infusion; D) 15 mg/M2/day X 4, 60-min infusion. Pharmacokinetic studies using HPLC technique were done in nine patients. All patients have since died and autopsies were performed in nine patients. Two major nonhematopoietic toxicities were encountered and were dose-schedule dependent: hemorrhagic colitis (six of six courses in Schedules A and B; two of seven in Schedules C and D), and hepatic dysfunction (five of six in Schedules A and B; two of seven in Schedules C and D). Histopathologic evidence of venocclusive disease of the liver was present in four of five autopsies in Schedules A and B, and two of four in Schedules C and D. One patient died as a result of liver failure associated with submassive hepatic necrosis. Saturation kinetics described by other investigators cannot be confirmed by our pharmacokinetic analyses in nine patients. Severe nonhematopoietic toxicities of mitomycin-C were found at three times the conventional dose; thus, this drug is assessed as not being clinically useful as a single agent in ABMT.

Adult↗
PubMed1985

Cancer of the anal canal. Model for preoperative adjuvant combined modality therapy.

An analysis of preoperative multimodality adjuvant therapy with 5-fluorouracil, mitomycin-C, and radiation therapy revealed that 38 of 45 patients (84 percent) treated were rendered free of cancer after chemotherapy/radiation therapy. No recurrence of tumor has been noted in those patients rendered free of disease by the preoperative treatment. Seven patients (15 percent) with residual macroscopic or microscopic cancer after preoperative therapy have had recurrence, all in distant sites. These seven patients have died from the disease. The prognosis for patients in this series depended on the success of the preoperative therapy in eradicating all tumor prior to surgery. Mitomycin-C and 5-fluorouracil are cytotoxic for local disease and for microscopic distant disease as well. Abdomino-perineal resection is unnecessary for patients whose primary tumor is eradicated by the preoperative therapy. The role of the relatively low dose of radiation therapy needs to be further defined.

Adult↗
PubMed1985

Carboplatin: a new platinum analog in the treatment of epidermoid carcinoma of the esophagus.

Thirty-one patients with advanced epidermoid carcinoma of the esophagus were treated with carboplatin (CBDCA), a second-generation cisplatin analog. Thirty patients were evaluable for response. Major responses (complete response) were seen in two patients (7%; 95% confidence limits, 1%-20%). The median survival from initiation of the protocol was 3 months (range, 0.1-16). Neither renal dysfunction nor emesis was a significant problem with CBDCA; hematologic toxicity was dose-limiting. Thrombocytopenia was more marked than leukopenia. CBDCA is a well-tolerated cisplatin analog that produced two complete responses in patients with advanced epidermoid carcinoma of the esophagus, where such responses are rarely observed. Although the observed response rate was only 7%, the 95% confidence limits overlap those previously reported for cisplatin (12%-31%).

Adult↗
PubMed1984

Cisplatin. An active drug in the treatment of disseminated gastric cancer.

Cis-diamminedichloroplatinum (DDP) was administered at 100 mg/m2 intravenously bolus with every 3-week schedule in patients with measurable and nonmeasurable incurable gastric cancer. Twenty patients were treated, 12 with measurable and 8 with nonmeasurable disease. Four of the 12 (33%) patients with measurable lesions had objective remissions. One remission was complete, lasting 60+ weeks. Patients with nonmeasurable disease were not eligible for response evaluation; they were followed for toxicity and survival. Hematologic, renal, and gastrointestinal toxicities were similar to those reported in other patient populations receiving DDP. Neurotoxicity proved to be dose limiting in two patients. The median survival was 38+ weeks for responders, 24 weeks for all patients, and 13 weeks for those 8 patients with nonmeasurable disease. DDP should be considered an active drug against gastric cancer. A better understanding of the dose response relationship for DDP in gastric cancer is necessary before the best dose and schedule can be chosen for DDP in combination with other active agents.

Adenocarcinoma↗
PubMed1984

Preoperative chemotherapy and radiation therapy for patients with cancer of the esophagus: a potentially curative approach.

Twenty-one patients with squamous cell cancer of the esophagus were entered into a pilot clinical trial using preoperative chemotherapy (5-fluorouracil and cis-platinum) and radiation with the intent of improving cure rate and survival. After the preoperative treatment was complete, 15 patients (71%) were resected for cure. Seven (47%) of 15 had no histologic evidence of cancer in the resected esophagus, but two of these had microscopic cancer in resected lymph nodes. The median survival for all patients entered in the trial was 18 months, whereas for those with no cancer in the resected esophagus the median survival was 24 months. The six patients who either refused surgery (two patients) or were unresectable at surgery (four patients) died within nine months. Our conclusion in this trial is that survival and potential cure are clearly linked to successfully clearing the esophagus and nodes of histologic evidence of tumor through preoperative treatment.

Adult↗
PubMed1983

Combined preoperative radiation and chemotherapy for squamous cell carcinoma of the anal canal.

Twenty-eight patients with squamous cell carcinoma of the anal canal were treated by preoperative radiation therapy and chemotherapy. The radiation therapy was given for 3000 rad (30 Gy) at 200 rad per day, 5 days a week, to the primary tumor with margin and to the pelvic and inguinal lymph nodes. Chemotherapy was given in the form of 5-fluorouracil infusion 1000 mg/m2 on days 1-4 of the radiation therapy and repeated on days 29-32 of the treatment regimen. Mitomycin C was given in the form of intravenous bolus for 15 mg/m2 on day 1. Surgery was done 4-6 weeks following the last day of radiation treatment. Twelve patients underwent anteroposterior resection, and seven of the 12 had no residual tumor in the surgical specimen, while one patient had microscopic tumor only. An additional 14 patients had complete clinical disappearance of their tumor, and, on excision of the scar, it was found free of microscopic cancer. Two other patients are clinically free of tumor but had no biopsy after therapy. While transient proctitis leukopenia and thrombocytopenia were moderate to severe, no serious complications were observed in these patients. Twenty-two patients are free of tumor and alive one to eight years after treatment. One patient died a cardiac death without tumor four years after surgery. Four patients, all with residual tumor in the specimen, have died of cancer. Their primary lesions were more than 7 cm in maximum diameter at initial examination. One patient died of disseminated disease with no local recurrence after abdominal perineal resection.

Adult↗
PubMed1983

Management of malignant bronchoesophageal fistulas.

Twenty-four patients with a bronchoesophageal fistula due to a malignant lesion were seen during the eight years from 1974 to 1981. Twenty of the patients had carcinoma of the esophagus, and four patients had carcinoma of the lung. All three patients who had a Celestin tube inserted had gastric reflux, and in two, the fistula was not completely occluded. Four patients who had a cervical esophagostomy, feeding jejunostomy and ligation of the gastroesophageal junction died in the immediate postoperative period. The best palliative result was achieved in 17 patients who had a bypass of the fistula with the stomach. Fourteen had a substernal gastric bypass to the cervical portion of the esophagus, and three patients had a gastric bypass to the upper thoracic portion of the esophagus by way of a right thoracotomy. Although the operative deaths occurred in six of 17 patients, the surviving patients resumed oral feeding within ten to 14 days after operation, and the pneumonias cleared. These patients had, by far, the best palliative result. We, therefore, advocate substernal or intrathoracic bypass of the bronchoesophageal fistula as soon as the general condition of the patient permits.

Adult↗
PubMed1981

Complete eradication of squamous cell carcinoma of the esophagus with combined chemotherapy and radiotherapy.

Chemotherapy (with 5-fluorouracil and either mitomycin-C or cis-platinum) combined with radiotherapy was used either for palliation or as preoperative therapy in 67 patients with squamous cell carcinoma of the esophagus. In 25 patients having chemotherapy and 5000-6000 rads, good local palliation was obtained in 11 (49%) without surgery. In the remaining 25 patients, swallowing was restored with a variety of procedures (primarily Celestine tube or gastric bypass). The average survival time was seven months and two patients are still alive at 9 and 12.5 months. Of 42 patients receiving preoperative chemotherapy and radiotherapy, 35 had surgery. Of these, 13 (37%) had complete eradication of their tumors with no histologic evidence of carcinoma in the resected esophagus or associated lymph nodes. In another six (17%), the only evidence of tumor was small microscopic foci of cancer cells in the wall of the esophagus. The 6-, 12-, and 24-month survival rates for patients having surgery after the combined preoperative chemotherapy and radiotherapy were 83 per cent, 52 per cent, and 30 per cent, respectively. These results are far superior to those previously obtained.

Adult↗
PubMed1981

Cis-diamminedichloride platinum(II), an effective agent in the treatment of epidermoid carcinoma of the esophagus. A preliminary report of an ongoing Southwest Oncology Group study.

The southwest oncology group tested cis-platinum, given in 28-day courses of 50 mg/m2 twice, a week apart, in patients with epidermoid carcinoma of the esophagus. Currently 19 patients entered on the study are evaluable for response (15 fully evaluable). Of these, two attained complete disappearance of tumor and four had partial responses. Of the remainder, two had stable disease lasting in excess of 90 days. Hematologic toxicity has been minimal except that three patients required multiple blood transfusions for anemia not due to blood loss. Of 21 patients currently evaluable for renal toxicity, nine had mild, and three had moderate azotemia. These results suggest that, unlike what has been believed in the past, squamous cell carcinoma of the esophagus is not a chemotherapy-resistant tumor. Further evaluation of cis-platinum alone and in combination with radiotherapy and surgery are in progress.

Carcinoma, Squamous Cell↗
PubMed1981

Eradication and palliation of squamous cell carcinoma of the esophagus with chemotherapy, radiotherapy, and surgical therapy.

Between April, 1977, and March, 1981, 86 unselected patients with proved squamous cell carcinoma of the esophagus were treated with a combination of chemotherapy and radiotherapy followed by operation whenever feasible. The preoperative chemotherapeutic agents used initially were 5-fluorouracil, and mitomycin C. After December, 1979, cis-platinum was used instead of mitomycin C. Radiotherapy (3,000 rads) of the tumor was begun at the same time as the chemotherapy. An esophagectomy was performed on suitable candidates 3 to 4 weeks after the chemotherapy and radiotherapy were completed. The mucosal lesion disappeared in 69 of the 86 patients, and dysphagia was relieved at least temporarily in 57 of 62 patients. Recurrent dysphagia resulting from fibrosis at the tumor site caused a secondary stenosis in 11 patients. Excellent palliation was obtained in five patients with bronchoesophageal fistulas who had an initial substernal gastric bypass followed by chemotherapy and radiotherapy. Of the 48 patients who had an esophagectomy, 15 (31%) had no tumor in the resected specimen. Eleven of these 15 patients are still alive with no evidence of disease. All patients with a lesion less than 5.0 cm in length had complete regression of the tumor. We believe that this combination of chemotherapy, radiotherapy, and surgical therapy provides excellent palliation, increases resectability, and has a potential for cure.

Adult↗
PubMedDate not supplied

Quantitation of intratumoral thymidylate synthase expression predicts for resistance to protracted infusion of 5-fluorouracil and weekly leucovorin in disseminated colorectal cancers: preliminary report from an ongoing trial.

A clinical trial for patients with measurable, disseminated colorectal cancer is being conducted to determine: (1) if intratumoral expression of thymidylate synthase (TS) affects response to protracted-infusion 5-fluorouracil (5FU); and (2) whether intratumoral expression of TS increases when clinical resistance is found after response to 5-FU. Polymerase chain reaction technology is employed to determine TS expression. Using beta-actin as an internal standard, TS expressions for 26 patients range from 0.5 x 10(-3) to 22.6 x 10(-3). Currently, 22 patients are evaluable for response and TS quantitation of their measurable tumour. 8 patients (36%) have had partial responses; 3 responding patients had been previously treated with 5-FU. A strong statistical association between TS expression and resistance to therapy has been found (P = 0.004). No patient with TS expression of 4.0 x 10(-3) or greater has responded. On average, patients previously treated with 5-FU have slightly higher levels of TS expression in their measurable tumours (P = 0.4). Whether responding patients will develop increased expressions of TS upon clinical progression of their cancer remains to be determined. Confirmation of these results in a larger cohort could lead to a scientific rationale for deciding upon specific therapy for patients with disseminated colorectal cancers.

Adult↗