Phase II trial of piroxantrone in gastric carcinoma. A Southwest Oncology Group study.

Twenty-one evaluable patients with advanced gastric adenocarcinoma were treated with piroxantrone at a dose of 150 mg/m2 intravenously every 21 days. One objective response was seen for an overall response rate of 5% (95% confidence interval 0-24%). Toxicities of grade > or = 3 were primarily hematologic and seen in 13/21 patients. Piroxantrone has minimal activity against gastric adenocarcinoma and no further investigation of this agent on this schedule in this disease is recommended.

Thyroid and parathyroid cancer.

The epidemiology, etiology, pathology, and management of thyroid and parathyroid carcinoma are discussed. Emphasis is placed on the clinical differences in the management and treatment of the various histologic subtypes of thyroid cancer. The biologic and prognostic differences among the various histologic types of thyroid cancer and their relationship to age are stressed.

1 alpha,25 Dihydroxyvitamin D3 and mononuclear phagocytes: enhancement of mouse macrophage and human monocyte hydrogen peroxide production without alteration of tumor cytolysis.

1 alpha,25 dihydroxyvitamin D3 (1,25 D3) is known to interact with hematopoietic cells. The purpose of this study was to determine the effect of 1,25 D3 on hydrogen peroxide (H2O2) production and tumor cell killing by mouse peritoneal macrophages and human blood monocytes. Enhanced monocyte and macrophages phorbol myristate acetate (PMA)-stimulated H2O2 production was observed at concentrations of 0.13 to 130 nM 1,25 D3 and and was maximal at 1.3 nM. At concentrations of 100 U/ml, gamma interferon (IFN-gamma) alone had a similar effect but, in combination with 1,25 D3, there was no cooperative effect. At concentrations ranging from 0.13 to 130 nM, 1,25 D3 failed to augment tumor cell lysis by macrophages from peptone-injected normal or bacillus Calmette-Guerin (BCG)-infected mice, or by blood monocytes from normal humans. Our results indicate that 1,25 D3 can activate the monocyte and macrophage for H2O2 secretion without concomitant activation for tumor cell killing.

Thyroid and parathyroid cancer.

The epidemiology, etiology, pathology, and management of thyroid and parathyroid carcinoma are discussed. Emphasis is placed on the clinical differences in the management and treatment of the various histologic subtypes of thyroid cancer. The biologic and prognostic differences among the various histologic types of thyroid cancer and their relationship to age are stressed.

Acute myeloblastic leukemia in paroxysmal nocturnal hemoglobinuria. Evidence of evolution from the abnormal paroxysmal nocturnal hemoglobinuria clone.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder in which the blood cells demonstrate aberrant interactions with serum complement. In part, this is due to the absence of the complement regulatory protein, decay accelerating factor (DAF). A small number of patients with PNH have gone on to develop acute nonlymphocytic leukemia, which is thought to arise from the injured marrow as a second hematopoietic disorder. We have studied a patient with PNH who developed acute myeloblastic leukemia (AML); the blasts from this patient were found to lack DAF as measured by polyclonal antibody binding and fluorescence flow cytometry as well as by immunoblotting. The blasts from 11 other patients with AML bound anti-DAF antibody in amounts similar to normal mononuclear cells from healthy donors. Cells of the human leukemia cell lines HL-60, K562, U937, and HEL also bound anti-DAF antibody. In addition to DAF deficiency, blasts from the PNH patient had undetectable alkaline phosphatase activity, in contrast to human leukemia cell lines. These data suggest that the leukemic cells of the PNH patient arose out of the PNH clone and that AML in the setting of PNH is not a separate disorder.

Isolated anterior chamber relapse in acute monoblastic leukemia.

A case of acute monoblastic leukemia relapsing in the anterior chamber of the eye is described. Despite rigorous evaluation, no systemic or central nervous system involvement was detected. All previously reported cases of anterior chamber infiltrates in AML have had coexistent systemic or central nervous system disease.

Acute lymphoblastic leukemia of Burkitt's type (L3 ALL) with 8;22 and 14;18 translocations and absent surface immunoglobulins.

A 57-year-old woman presented with L3 acute lymphoblastic leukemia demonstrating typical Burkitt's type morphology. Cytogenetic analysis revealed one of the variant translocations seen in Burkitt's lymphoma [t(8;22)] and a 14;18 translocation. Surface marker data at presentation and at autopsy demonstrated several B-cell markers, but absent surface immunoglobulins. The case presented here reveals a possible cytogenetic link between Burkitt's lymphoma and follicular center-cell lymphoma, and illustrates a variant surface marker profile for Burkitt's lymphoma.

Radiologic manifestations of small-bowel toxicity due to floxuridine therapy.

Floxuridine (5-FUDR) is an antipyrimidine used in the treatment of metastatic colorectal carcinoma. Bowel toxicity, manifested predominantly by diarrhea and abdominal pain, is one of the main complications of 5-FUDR therapy. Six patients who had received 5-FUDR infusion either by hepatic arterial or systemic intravenous routes subsequently developed severe diarrhea and were evaluated by small-bowel series. Radiographic changes were largely confined to the ileum. In four of six patients, the entire ileum or its more distal part was markedly narrowed. In the other two patients, changes consisted of thickening or effacement of the mucosal folds in the distal ileum. The symptoms of all six patients resolved after discontinuation of 5-FUDR therapy. This was accompanied by improvement in the radiographic appearance of the ileum in three patients who underwent a subsequent small-bowel series. The finding of reversible ileal changes, particularly extensive or segmental narrowing, seems to be a characteristic radiographic feature of bowel toxicity due to infusional 5-FUDR delivered by either the intraarterial or the systemic route.

A reversible enteropathy complicating continuous hepatic artery infusion chemotherapy with 5-fluoro-2-deoxyuridine.

This article describes two patients with hepatic metastases from colorectal cancer in whom a reversible enteropathy developed during the administration of hepatic artery infusion chemotherapy with 5-fluoro-2-deoxyuridine (5-FUdR) via an Infusaid Series 400 pump (Infusaid Corp., Sharon, MA). Both patients had severe diarrhea and signs that suggested small bowel obstruction. Barium studies revealed a distinctive radiologic appearance of severe narrowing of the ileum associated with complete loss of normal mucosal patterns. Results of an extensive evaluation for an infectious or toxin-related enterocolitis were negative. Perfusion studies confirmed the appropriate position of the catheters and revealed no extrahepatic perfusion. Systemic shunting of the 5-FUdR through the liver or tumor bed is postulated as the primary event, with the small bowel manifesting the major toxicity.