Lora Weiselberg

Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced transitional cell carcinoma of the urothelium. Efficacy and patterns of response and relapse

Of 133 patients with advanced urothelial tract cancer given methotrexate (MTX), vinblastine (VBL), Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (DDP) (M‐VAC regimen), significant tumor regression occurred in 72% ± 8% of 121 with transitional cell carcinoma (TCC) evaluable for response. Complete remission (CR) was achieved in 36% ± 9% of patients, of whom 11% required the addition of surgical resection of residual disease. Although 68% of CR patients have relapsed, CR median survival will exceed 38 months compared with 11 months for partial (36%) and minor (6%) responders, and 8 months for nonresponders: 2‐year and 3‐year survivals were 68% and 55%, respectively, versus 0% to 7% for the remaining patients. Sixteen percent of responders developed brain lesions, half of whom had no systemic relapse at the time of progression. Three patients with non‐TCC histologies did not respond. In 32 patients who had pathologic restaging, the clinical (T) understaging (T < pathologic [P] restaging) error was 35%. Although all metastatic sites showed evidence of tumor regression, CR was noted more frequently in lung, in intraabdominal lymph nodes and masses, and in bone (24% to 35%); the rate for hepatic lesions was 15%. There were 52% of 21 N3–4Mo patients who achieved CR versus 33% of 100 with No‐+M+ lesions. Toxicity was significant with 4 (3%) drug‐related deaths, 25% incidence of nadir sepsis, 58% ⩾ 3+ myelosuppression, and 49% with mucositis. Responsiveness of metastasis in various sites, patterns of relapse, and the usefulness of the new CR response criteria are reported, as is the current status of cisplatin and methotrexate combination regimens. Cancer 64:2448–2458, 1989.

Dysmyelopoietic syndrome: Current concepts

Compte-rendu de seminaire. Caracteristiques morphologiques de la myelodysplasie (avec microscopie electronique). Modifications cytogenetiques. Evaluation clinique

Acquired idiopathic sideroblastic anemia: A new chromosomal abnormality

We describe two patients with acquired idiopathic sideroblastic anemia and a terminal deletion of chromosome No. 11. In spite of the marked chromosomal abnormality neither patient has developed acute leukemia.

Adjuvant Therapy of Stage Ii Breast Cancer Treated with Cmfvp, Radiation Therapy and Vath Following Lumpectomy A Pilot Trial

A pilot study was undertaken to assess the feasibility, toxicity, and efficacy of combined radiation therapy and chemotherapy in the adjuvant treatment of node-positive, Stage II patients with breast carcinoma who had undergone lumpectomy. Therapy consisted of three phases, starting with a six-week CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone) induction, followed by radiation therapy to the breast, and concluding with four cycles of VATH (vinblastine, Adriamycin, thiotepa, Halotestin). Twenty-seven patients were entered with an average age of 51.5 years (median 50 yrs) and a mean follow-up of 46.2 months. Twenty-three patients (85.2%) are alive and 19 (70.3%) disease free. There were no ipsilateral local recurrences. Cosmetic results were good to excellent in 26/27 patients. The doses of VATH were not compromised by the prior therapy. The regimen was found to be tolerable and is a reasonable approach in the adjuvant treatment of this particular patient population.

Phase I trial of intravenous vinzolidine (LY 104208) given on a biweekly dosing schedule

SummaryVinzolidine (VZL) is a semisynthetic vinca alkaloid with broad antitumor activity in animal models of malignancy but had unpredictable toxic effects when given orally to humans. To minimize the toxic effects due to potential erratic gastrointestinal absorption, this drug was restudied in man as an intravenous preparation given as a rapid injection every two weeks. The maximum tolerated dose (MTD) on this schedule was 9.0 mg/m2 with unpredictable leukopenia (usually occurring 5–14 days post treatment but appearing erratically), constipation, paralytic ileus, and inappropriate ADH syndrome as major toxicities. Nonhematologic toxicities were dose-limiting. Repetitive dosing at two week intervals was associated with leukopenia at D 14–15 in some but not all patients treated above 5.0 mg/m2 precluding further treatment on schedule. In contrast, the oral MTD of this agent in our prior studies was 45 mg/m2 with no evidence of delayed leukopenia. Intrapatient variability of toxicity was small; interpatient variability of toxicity was substantial and did not correlate with prior therapy. Because of the presence of delayed hematologic toxicity on repetitive dosing schedules, intravenous VZL should be given on a dosing schedule longer than 14 days. No antitumor activity was seen in this study.

Anaphylactoid reaction due to AZQ.

AZQ, 1,4 cyclohexadiene-l,4 dicarbonic acid, 2,5-bis (1-azirindinyl)-3,6-dioxodiethylester (NSC 182986) is a lipophilic agent with antitumor activity noted in phase II trials [2]. We observed a life-threatening, immediate anaphylactoid reaction in a patient receiving AZQ by intermittent IV bolus every 3 weeks as part of a national phase II trial in non-oat cell carcinoma (CALGB 8046). The patient is a 65-year-old white female with large cell carcinoma of the lung, who tolerated rapid infusion of AZQ over 30 min well except for mild nausea and anemia. At the time of her ninth cycle, she developed local hives at the site of the catheter, which were felt to be due to the antiseptic skin cleaning solution. She was not receiving any other medication. At the time of the tenth cycle, the patient with PS O received approximately 5 mg AZQ (lot # BV 81-207) with N , N-dimethylacetamide solvent (DMA lot # BV 81-223). She developed the sudden onset of cyanosis, wheezing, hypotension (BP systolic 80), and diaphoresis. Rapid IV infusion of fluid, aminophylline, corticosteroids, and SC epinephrine reversed the shock reaction within 30 rain, with full recovery in 2 h. Antineoplastic agents have been previously associated with immediate hypersensitivity reactions with L-asparaginase being the most common causative agent [1, 3]. In this case, the patient had no other medication except the AZQ dissolved in DMA. The incidence of this allergic reaction may be rare, as in the Cancer and Leukemia Group B trials of AZQ (a total of 200 patients) (Weinberg, unpublished work) only this patient manifested a life-threatening allergic reaction, giving an incidence at the 95% confidence level of 0 -1 .5%.

Electron microscope cytochemical analysis of chronic myelocytic leukemia: A case report

A patient with Philadelphia chromosome positive CML was studied to characterize the blast transformation. Peripheral blood and bone marrow at the onset of the blast crisis were evaluated with cytochemistry, chromosome analysis, cell surface markers, terminal transferase assay, and electron microscopy. Although light microscopic examination and cytochemistry suggested lymphoblastic morphology, ultrastructural cytochemistry demonstrated the myelomonocytic features of the transformation. This study suggests that electron microscopic cytochemistry is useful in evaluating the heterogeneous nature of the blast phase of CML.

Pharmacokinetic evaluation of zeniplatin in humans

Zeniplatin, a more water-soluble organoplatinum than cisplatin, was evaluated for clinical pharmacology in the context of a phase II trial in previously treated patients with ovarian carcinoma. A total of 12 patients were given zeniplatin at 120 mg/m2 by rapid intravenous infusion over 90 min, with both blood and urine being sampled. All platinum moieties were analyzed in whole blood, plasma, plasma ultrafiltrate, and urine by atomic absorption, and free zeniplatin was analyzed in plasma ultrafiltrate by specific high-performance liquid chromatography (HPLC). In a comparison of the platinum-time concentration curve, AUC (area under the curve) values indicated that approximately 90% of platinum moieties were bound to circulating plasma proteins. There was no evidence of drug accumulation after repetitive dosing. The terminal half-life (t1/2) of this drug in plasma ultrafiltrate (3.7–7.2 h.) as measured by HPLC was slightly longer than that of carboplatin, whereas total platinum moieties in plasma displayed a longt1/2 (124–154 h). Approximately 60% of platinum moieties could be recovered in the urine within 24 h. These findings suggest that zeniplatin has a pharmacokinetic profile similar to that of carboplatin.