Sequential chemotherapy and radiotherapy for squamous cell esophageal carcinoma.

A Phase II study of sequential chemotherapy with 5-fluorouracil and cisplatin followed by radiotherapy was initiated to see whether the use of two therapies sequentially could have an effect on response rate. Thirteen patients with advanced squamous cell carcinoma of the esophagus were treated with 1,000 mg/m2/day 5-fluorouracil days 1-5 continuously and 100 mg/m2 cisplatin on day 1. An average of four cycles (range, one to nine) were given every 28 days; 11 patients received more than three cycles. The radiation consisted of 60 Gy over 6-8 weeks. There was only one (8%) complete response (CR) and 11 (85%) partial responses (PRs). Restaging after radiation revealed no conversion of PR to CR. Median survival was 39 weeks (range, 6-208+). Chemotherapy alone or its use sequentially with radiotherapy is inadequate, and newer approaches are needed to to improve survival.

Porocarcinoma of the heel. A case report with unusual histologic features.

BACKGROUND: Eccrine porocarcinoma is an uncommon neoplasm of the intraepidermal sweat gland duct. METHODS: A case of porocarcinoma of the right heel in a male age 51 years is described with a review of pertinent literature. The surgically excised neoplasm was evaluated by routine histology and transmission electron microscopy. RESULTS: The porocarcinoma showed extensive nuclear pleomorphisms with frequent, multinucleated tumor giant cells, focal epidermotrophic spread within the epidermis, a peripheral, eccrine syringofibroadenoma-like growth pattern, and an origin in a contiguous eccrine poroma. Ultrastructurally, the squamous tumor cells contained rare intracytoplasmic lumens. CONCLUSIONS: The extensive nuclear pleomorphism with frequent tumor giant cells was an unusual feature of the porocarcinoma. Its epidermotrophic spread within the epidermis and its origin in a contiguous eccrine poroma supported the diagnosis of porocarcinoma. The eccrine syringofibroadenoma-like growth pattern in the periphery of the tumor was a unique and previously undescribed feature of the porocarcinoma. The presence of intracytoplasmic lumens in squamous tumor cells mimicked embryonic development of the intraepidermal sweat gland duct.

Nonsurgical closure of esophago-respiratory fistulas: role for the somatostatin analogue octreotide acetate?

Esophago-respiratory fistulas (ERF) do not close spontaneously and are uniformly fatal. A somatostatin analogue (octreotide acetate) was used in three consecutive patients to promote the closure of ERF. In 2 patients with esophageal cancer, treatment with octreotide acetate was associated with fistula closure in 30 and 46 days, respectively. In a third patient with virally-induced ERF, treatment was associated with improvement of the inflammation of the fistula before the patient's death from pulmonary aspiration after 40 days of treatment. These preliminary observations suggest that octreotide acetate treatment of ERF should receive further investigative scrutiny.

Closure of tracheoesophageal fistulas with primary chemotherapy in patients with esophageal cancer.

BACKGROUND: In patients with tracheoesophageal fistula, radiation is thought to be contraindicated because cytoreduction enlarges the size of the fistula. The same caveat should also apply to cytoreduction with chemotherapy, but there are few data addressing this issue. METHODS: The records of 16 patients with esophageal cancer who received chemotherapy in 1991 were evaluated in the Medical Oncology Section of the Veterans Administration Medical Center, Washington, DC. All patients were staged radiographically and endoscopically. Four of these 16 were seen initially with or developed tracheoesophageal fistulas during therapy. Two patients whose fistulas closed during chemotherapy are presented. RESULTS: All four patients with tracheoesophageal fistulas had midesophageal squamous cell carcinomas. Objective complete responses with closure of tracheoesophageal fistulas occurred in two of four patients after three and four cycles of chemotherapy, respectively. One of these fistulas first developed, then healed during treatment, whereas the other presented at the time of diagnosis with fistula. CONCLUSION: The findings indicated that patients with tracheoesophageal fistulas should not be excluded from chemotherapy solely on the basis of having this condition. The treatment of patients with tracheoesophageal fistulas with chemotherapy needs to be reexamined.

Nocardiosis after corticosteroid therapy for malignant thymoma.

BACKGROUND: Nocardia asteroides is an opportunistic infection caused by an aerobic actinomycete, which, in the immunocompromised host, can be associated with severe invasive disease with a predilection for the brain. METHODS AND RESULTS: The authors describe a 62-year-old man with a malignant thymoma that was clinically responsive to oral prednisone. N. asteroides sepsis subsequently developed, leading to his death. CONCLUSIONS: Nocardiosis should be considered a potential pathogen in this immunocompromised setting.

Evaluation of the carcinogenic potential of toluidine blue O in the hamster cheek pouch.

Toluidine blue O has been shown to have clastogenic and mutagenic effects when tested in vitro, suggesting that it may be a carcinogen. Because this might compromise its use for cancer screening, the carcinogenic potential of this dye was investigated in the hamster cheek pouch, an established in vivo carcinogenesis model. Male hamsters were divided into seven groups at age 5 weeks. The right pouches of four groups were painted three times weekly with 2% toluidine blue or the vehicle for toluidine blue, in conjunction with submaximal applications of 9,10-dimethyl-1,2-benzanthracene (DMBA) (groups II and III, 0.5% twice weekly), and groups IV and V, 0.1% three times weekly). The right pouches of two groups received DMBA only (group I, 0.5% three times weekly, the standard maximal amount, and group VI, 0.1% three times weekly). Group VII received toluidine blue (right pouches) and toluidine blue vehicle (left pouches) three times weekly. The extent of carcinomas and other abnormalities (scored histologically) did not differ among groups receiving the same amount of DMBA with and without toluidine blue or vehicle, and no abnormalities were seen in the pouches from group VII. These results demonstrate no effect of toluidine blue as a carcinogen, cocarcinogen, or promoter.

Vitamin E in the treatment of chemotherapy-induced mucositis.

PURPOSE: To determine the efficacy of vitamin E in the treatment of chemotherapy-induced mucositis in patients with malignancy. PATIENTS AND METHODS: A randomized, double-blind, placebo-controlled study was performed to evaluate the efficacy of topical vitamin E in the treatment of oral mucositis in patients receiving chemotherapy for various types of malignancy. A total of 18 patients, 17 of whom had solid tumors and one with acute leukemia, were included in this study. Lesions were observed daily prior to and 5 days after topical application of either vitamin E or placebo oil. RESULTS: Six of nine patients receiving vitamin E had complete resolution of their oral lesions. In eight of nine patients who received placebo, complete resolution of their oral lesions was not observed. This difference is statistically significant (p = 0.025 by Fisher's exact test). No toxicity was observed in this study. CONCLUSION: These results suggest that vitamin E may be an effective therapy in patients with chemotherapy-induced mucositis.

Recent clinical experience with dronabinol.

Dronabinol, delta-9-tetrahydrocannabinol in sesame oil, has been used for several years as an antiemetic for patients receiving cancer chemotherapy. In combination studies with prochlorperazine, enhancement of efficacy, as measured by duration of episodes of nausea and vomiting and by severity of nausea, has been found. The incidence of psychotropic effects from dronabinol appears to be decreased by concomitant administration of prochlorperazine. In open pilot studies, dronabinol caused weight gain in seven of ten patients with symptomatic HIV infection. In both HIV and cancer patients, dronabinol improved appetite at a dose which was well tolerated for chronic administration.

New directions in managing chemotherapy-related emesis.

The author reviews the physiology of the various types of emesis and the factors that influence chemotherapy-induced nausea and vomiting, including both patient-related factors and those related to treatment. He then enumerates and describes the antiemetic agents now available, ranging from phenothiazines to cannabinoids and serotonin (5-hydroxytryptamine) antagonists; explains how they might best be used; and outlines the probable future direction for antiemetic studies.

Continuous intravenous infusion of morphine for severe dyspnea.

We describe eight patients who had terminal lung cancer causing severe dyspnea unrelieved by oxygen, nonnarcotic drugs, or intermittent bolus narcotics. We treated these patients with continuous intravenous infusion of morphine, beginning with bolus IV injections of 1 or 2 mg of morphine every 5 to 10 minutes until the patient reported relief. A continuous morphine infusion was then started, with the hourly dose equal to 50% of the cumulative bolus dose. Vital signs, degree of sedation, and blood gases were serially followed. Six patients achieved good dyspnea relief, one had moderate relief, and one had a poor response. Variable changes were noted in the PaO2, whereas PaCO2 steadily increased in five of seven patients, and pH decreased in six. There was little change in systolic blood pressure or pulse, and only one individual had less than 10 respirations per minute. The major side effect of treatment was sedation, treated by temporarily discontinuing morphine until the patients' mental status improved and then restarting the infusion at a 50% lower hourly morphine dose. Mean time of study was 30 hours (range 16 to 87 hours). Seven of the eight study patients died during treatment. Whether morphine therapy shortened survival is uncertain. We conclude that continuous morphine infusion is effective therapy for severe dyspnea. The treatment is ethically justified. Relief of suffering is the primary goal of therapy, and less risky treatments are unavailable.

H-ras-1 polymorphism in leukemia.

We have examined leukocyte DNAs obtained from 21 patients with various types of leukemia for the Sacl polymorphism of H-ras-1. The patients included ten with B-lineage leukemia, two with T-cell leukemia, and nine with acute myelogenous leukemia. Using a genomic probe for H-ras-1 in Southern hybridizations, we found that 78% of the DNA from leukemias of myeloid origin were heterozygous. In contrast, only three of ten B-cell-derived leukemias showed heterozygosity. This difference in the number of heterozygotes vs. homozygotes in the two patient samples studied is statistically significant (P = 0.04 by Fisher's exact test). These results suggest the possibility that the H-ras-1 allelic pattern that is associated with acute myelogenous leukemia is distinct from that found in B-cell-derived malignancies.

Problems in antiemetic trial design and interpretation.

Research in the control of chemotherapy-induced nausea and vomiting is a relatively new endeavor. Accurate assessment of clinical trial results assumes a sound study design, control for known variables, clear definitions, and reproducible assessment criteria. In most of these areas, antiemetic trials still lag behind cancer treatment trials. This paper reviews 44 antiemetic trials and discusses the state of the art in antiemetic research methodology, examining how a representative sample of investigators have addressed patient selection criteria, study design, and assessment parameters. Comparisons with the chemotherapy literature suggest approaches to improve the antiemetic literature and optimize our use of the data derived from it.

Thrombosis: the major Hickman catheter complication in patients with solid tumor.

Major complications of Hickman catheter placement (thrombosis and infection) were determined in 168 patients with solid tumor (lung, 79; head and neck, 56; esophagus, 24; and miscellaneous, 9). Catheter-related thrombosis was clinically detected in 22 individuals and was detected at autopsy in six (total 17 percent). The 17 percent figure underestimates the true incidence of thrombosis since only 25 percent of study patients had autopsies. Patients with adenocarcinoma of the lung constituted a high risk group. Nine of 20 (45 percent) of these patients had thrombosis compared to 25, 9, and 16 percent of patients with squamous cell cancers of lung, head and neck and esophagus, respectively (p less than 0.002). Three patients with thrombosis had pulmonary emboli and two died. Thrombosis occurred despite daily heparin catheter flushing. INfections occurred in 11 patients. One had suspected endocarditis, one had a subcutaneous tunnel infection, and nine had exit site infections. All responded to local or systemic antibiotics. Better methods to prevent thrombosis are needed.

Carotid sinus syndrome associated with an occult primary nasopharyngeal carcinoma.

A patient presented with syncope, and a diagnosis of carotid sinus syndrome was established. Further evaluation revealed a large nasopharyngeal carcinoma invading the left petrous bone. There were no cervical metastases. The tumor partially regressed with radiation therapy, and there was complete resolution of the carotid sinus syndrome, but the patient died three months later of metastatic disease. Autopsy confirmed petrous bone involvement by the mass but no cervical metastatic disease. This is the first reported case (to our knowledge) of malignancy-associated carotid sinus syndrome attributable to a primary nasopharyngeal carcinoma. The literature on malignancy-associated carotid sinus syndrome is reviewed, with emphasis on pathophysiology and treatment.

Simultaneous chemotherapy and radiotherapy for squamous cell lung cancer.

Simultaneous chemotherapy and radiotherapy was evaluated in 13 patients with inoperable, limited stage squamous cell lung cancer. The chemotherapeutic agents bleomycin, methotrexate, 5-fluorouracil, vinblastine, and cisplatin were administered on days 1 and 5 of two treatment cycles given 5 weeks apart. Radiation therapy was given in three 2-week cycles, the first two starting on the second day of each chemotherapy cycle and the third starting 3 weeks after the second course of radiation. The total dose was 5000-5500 rad (50-55 Gy) in 180 rad fractions. The objective response rate (complete response + partial response) was 85%, with 38% complete responders. Median survival was 7 months with two patients surviving 34 months, one with disease and one disease-free. Treatment toxicity was predominantly hematopoietic and renal. Two patients died with massive pulmonary hemorrhage while receiving treatment and a third patient died of acute respiratory failure 1 month after completing therapy. The severe toxicity and the failure to obtain long duration tumor control makes this regimen unsuitable for future use.

Lung cancer, tuberculin reactivity, and isoniazid.

We determined the incidence of tuberculosis in lung cancer patients with known tuberculin status. All patients received chemotherapy with or without radiation therapy, corticosteroid therapy, or both, and none received isoniazid prophylaxis. Positive tuberculin reactivity was found in 89 of the 257 patients; among these 89, tuberculosis developed in one patient before and in one patient after chemotherapy. Among the other 168 patients, one case of tuberculosis developed after chemotherapy. For all lung cancer patients, the incidence of tuberculosis was higher than age-specific and race-specific rates in a control population. The risk of tuberculosis was judged to be significantly higher in patients with positive than with negative tuberculin reactivity; among tuberculin reactors, however, the risk of tuberculosis was estimated to be less than the potential risk of isoniazid hepatotoxicity reported in the literature for patients in a similar age group. The median survival for tuberculin-positive lung cancer patients was 9.6 months. Because of the limited survival in these patients, and because of the high risk of isoniazid hepatotoxicity for patients in this age group, we do not recommend isoniazid prophylaxis for tuberculin-positive patients receiving chemotherapy for lung cancer.

Clearance of continuous intravenous morphine for severe cancer pain.

Four cancer patients with intractable pain received continuous morphine infusions in doses of 15-275 mg/h for a time period ranging from 4 to 27 days. Serum morphine concentrations were determined periodically following adjustments in infusion rates. As doses were changed and continued at static hourly rates, serum morphine concentrations were relatively constant 20 hours and beyond the time of the respective change, thus suggesting morphine elimination half-lives of less than or equal to 4 hours. High doses did not influence the time required to achieve steady-state concentrations. Steady serum morphine concentrations corresponded with hourly morphine doses in a parallel manner. High interpatient variabilities in clearances and steady-state serum morphine concentrations were noted. These data suggest that at morphine infusions up to 275 mg/h elimination pathways permit handling of increasing concentrations of morphine without nonlinear blood level increases. Also, marked interpatient and intrapatient variations in patient dose requirements were noted.