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Biomedical subjects

B J Lewis

Publications and source records attributed to B J Lewis.

At least 37 records · Page 2Linked to original sources

Third-line chemotherapy for resistant Hodgkin's disease with lomustine, etoposide, and methotrexate.

Thirty-two patients with recurrent Hodgkin's disease have been treated with an oral regimen employing lomustine (CCNU, 100 mg/m2 orally on Day 1); etoposide (VP-16, 100 mg/m2 orally on Days 1-3 and 21-23); and methotrexate (30 mg/m2 orally on Days 1, 8, 21, and 28). The regimen was repeated every 6 weeks. Most patients had been treated with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine); 20 had had prior irradiation. Lymph node was the predominant site of disease and the majority of patients had B symptoms. Four patients achieved complete response (13%), with a median duration of 33+ months, and 11 achieved partial response (34%), with a median duration of 5 months, for an overall response rate of 47%. The major toxic effect was severe myelosuppression, which occurred in six patients; there were no treatment-related deaths. This oral regimen was easy to administer in heavily pretreated patients with poor venous access and had minimal toxicity.

Administration, Oral↗

Toxicities and complications of implanted pump hepatic arterial and intravenous floxuridine infusion.

Toxicities and complications were prospectively analyzed in patients with liver metastases receiving hepatic intra-arterial (IA) and systemic intravenous (IV) floxuridine (FUDR) with the Infusaid (Intermedics-Infusaid Corp., Norwood, MA) implantable pump. Among 55 patients treated with IA FUDR (0.3-0.1 mg/kg/day X 14, every 28 days), elevations in liver enzyme values, not attributable to disease progression, developed in 96% of patients. Serious biliary toxicity occurred in 31 patients (56%). In 16, biliary sclerosis was documented radiographically and was diagnosed clinically in 15 additional patients. Ten patients were hospitalized for biliary toxicity, including five who required cholecystectomy for acalculous cholecystitis. Because of the high reported incidence of serious gastroduodenal toxicity after IA FUDR infusion, our procedure for hepatic arterial cannulation was designed to eliminate misperfusion of the stomach and duodenum with drug; none of our patients experienced FUDR-associated gastroduodenal ulceration or bleeding. Cyclic IV FUDR (0.05-0.15 mg/kg/day X 14, every 28 days) was administered to 31 participants of the Northern California Oncology Group trial (3L-82-1) of IV versus IA FUDR. Dose-limiting toxicity was diarrhea. Serious toxicities were: protracted diarrhea (three), dermatitis (two), tear duct stenosis (two), and stomatitis (two). Three patients were hospitalized for toxicity. No hematologic or biliary toxicity occurred. The optimal route for treatment of hepatic metastases with continuous FUDR infusion has not yet been established. Systemic IV infusion has low morbidity, but preliminary response data need to be substantiated in controlled clinical trials before there can be widespread clinical application. High response rates for IA infusion have been previously documented. Morbidity due to acalculous cholecystitis and gastroduodenal ulceration can now be avoided. Despite significant progress in characterization of hepatobiliary toxicity, it remains dose-limiting. Continuous IA FUDR infusion should remain under the aegis of dedicated treatment centers until standardized protocols with diminished toxicity are established.

Alkaline Phosphatase↗

Avoidance of gastroduodenal toxicity in patients receiving hepatic arterial 5-fluoro-2'-deoxyuridine.

Gastroduodenal inflammation and ulceration have been frequently observed in patients receiving continuous hepatic arterial infusions of 5-fluoro-2'-deoxyuridine (FUDR) for liver malignancy. Thirty-five patients with metastatic colon cancer received hepatic arterial FUDR administered with implanted infusion pumps. At surgery, particular care was taken to identify and divide those vessels arising from the hepatic arteries distal to the point of cannulation that supplied the superior border of the distal stomach and proximal duodenum. None of the patients developed signs or symptoms of gastritis or ulcer attributable to chemotherapy. We contend that gastritis and ulcer in patients receiving hepatic arterial FUDR are due to misperfusion of drug into the upper gastrointestinal tract and that these complications can be largely avoided by use of appropriate surgical techniques.

Colonic Neoplasms↗

Hematologic manifestations in homosexual men with Kaposi's sarcoma.

Peripheral blood and bone marrow findings are presented for six homosexual males with Kaposi's sarcoma. Cytopenia in one or more cell lines was common in this group of patients, including two individuals with pancytopenia. Bone marrow findings in all patients, while not specific, were similar in that adequate numbers of normal appearing erythroid, myeloid, and megakaryocytic elements were present. Mild plasmacytosis as well as reticulin fiber increase were common findings. No patient, at time of study, demonstrated marrow involvement with Kaposi's sarcoma. We conclude that depression of peripheral blood counts in these patients was not due to marrow underproduction, and discuss possible mechanisms for increased blood cell destruction.

Acquired Immunodeficiency Syndrome↗

Kaposi sarcoma and lymphadenopathy syndrome: limitations of abdominal CT in acquired immunodeficiency syndrome.

Abdominal computed tomography (CT) was performed in 31 patients with Kaposi sarcoma (KS) related to acquired immunodeficiency syndrome (AIDS), three patients with classic KS, and 12 patients with the newly described lymphadenopathy syndrome (LNS). The frequency, distribution, and appearance of lymphadenopathy and splenomegaly were similar in the AIDS-related KS and LNS groups. Rectal and perirectal disease was identified in 86% of the homosexual men studied; rectal KS could not be distinguished from proctitis on CT criteria alone. No CT abnormalities were seen in patients with classic KS. The CT demonstration of retroperitoneal, mesenteric, or pelvic adenopathy or of rectal or perirectal disease in patients with AIDS-related KS is not necessarily indicative of widespread involvement with the disease.

Acquired Immunodeficiency Syndrome↗

Hepatic arterial chemotherapy for colorectal cancer metastatic to the liver.

Hepatic metastases of colorectal origin are resistant to radiation and immunotherapy. Traditional intravenous chemotherapy produces responses in 10% to 30% of patients, and surgical resection is feasible in approximately 20% of patients who have a solitary or unilobar lesion. Infusion of cytotoxic agents into the hepatic artery, introduced 2 decades ago, is the most promising form of therapy for unresectable hepatic metastases. Fluorouracil, floxuridine, and mitomycin have been most commonly administered by hepatic arterial infusion. The recent development of a totally implantable pump has allowed prolonged ambulatory infusion of chemotherapeutic agents into the hepatic artery. We review the recent data on the pharmacology, therapeutic outcome, administration techniques, and complications of hepatic arterial chemotherapy. Future trials in this area should use uniform stratification variables and standardized criteria for evaluating response, time to progression, and survival.

Antineoplastic Agents↗

Persistent diffuse lymphadenopathy in homosexual men: endpoint or prodrome?

Seventy homosexual men with unexplained persistent diffuse lymphadenopathy enrolled in a prospective natural history study from November 1981 to November 1982. These men had demographic, clinical, and laboratory findings similar to those of homosexual patients with the acquired immunodeficiency syndrome. Pathologic examination of lymph node biopsies from 35 patients showed florid follicular hyperplasia. Despite benign reactive pathologic findings, most patients had constitutional symptoms and recurrent non-life-threatening infections. All had evidence of immune dysfunction with B-lymphocyte activation and inversion of the T-lymphocyte helper: suppressor ratio. To date, none of our patients has developed the more malignant manifestations of the acquired immunodeficiency syndrome. The lymphadenopathy syndrome may be an alternative phenotypic response to the "acquired immunodeficiency syndrome agent."

Adult↗

Complications of co-trimoxazole in treatment of AIDS-associated Pneumocystis carinii pneumonia in homosexual men.

In 8 of 18 homosexual men with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia (PCP) treated with intravenous co-trimoxazole (trimethoprim-sulphamethoxazole) apparent drug-related complications developed during the course of acute therapy. A symptom complex of fevers and increasing malaise, often with nausea and headaches, developed usually after 9 days of therapy at a daily dosage of 20 mg/kg of trimethoprim and 100 mg/kg of sulphamethoxazole. These symptoms were associated with a diffuse erythematous maculopapular eruption and peripheral cytopenias. A similar picture was noted in two children with suspected AIDS-associated PCP. The high frequency of adverse reactions to co-trimoxazole therapy for PCP seems to be characteristic of AIDS patients.

Acquired Immunodeficiency Syndrome↗

Chemotherapy in advanced Kaposi's sarcoma. Implications for current cases in homosexual men.

Kaposi's sarcoma has recently appeared in an aggressive form in young, previously healthy, homosexual men. The disease in these patients corresponds most closely to disseminated Kaposi's sarcoma common in areas of Africa. This and the underlying acquired immune deficiency in the current patients in the United States affect the choice of appropriate therapy. Because Kaposi's sarcoma in these patients is rapidly progressive, it often requires aggressive systemic therapy, but this can be difficult given the patients' susceptibility to opportunistic infections. Reports from Africa suggest that Kaposi's sarcoma is very responsive to several chemotherapeutic agents, but these data must be interpreted cautiously because of problems in study design and differences between cases in Africa and the United States. This report reviews the clinical classification of Kaposi's sarcoma and the reported results of chemotherapy in patients with advanced disease. Implications of this experience in the treatment of recent cases in the United States are discussed.

Acquired Immunodeficiency Syndrome↗

Hyperthermia and chemotherapy: preclinical considerations.

Malignant cells appear to be selectively sensitive to thermal injury. The precise mechanism of cell death after thermal exposure has not been established, but the phenomenon has been demonstrated by both in vitro and in vivo techniques. Synergy of hyperthermia and chemotherapy has been demonstrated for several agents, but in vitro results are not uniformly confirmed in vivo. In some agents (methyl-CCNU) no synergy was found in vivo. In others (adriamycin) synergy was only demonstrated at drug doses with intolerable toxicity. Studies of the effects of hyperthermia on drug pharmacokinetics are desirable for future clinical trial design.

Alkylating Agents↗