A phase II clinical trial of echinomycin in metastatic soft tissue sarcoma. An Illinois Cancer Center Study.

Echinomycin, a cyclic peptide in the family of quinoxaline antibiotics, was evaluated in patient with metastatic, soft tissue sarcoma not previously treated for metastatic disease. The starting dose of echinomycin was 1,200 mcg/m2 administered intravenously, once weekly x 4, followed by a two-week break. The protocol design called for dose escalation on subsequent cycles of therapy, but because of significant toxicity, dose escalation occurred in only 5 of 25 treatment cycles. Severe nausea and vomiting was the most common toxicity. No clinical responses were observed in the 12 evaluable patients. Echinomycin at this dose and schedule is inactive in metastatic soft tissue sarcoma.

Phase II study of amonafide in the treatment of patients with advanced squamous cell carcinoma of the head and the neck. An Illinois Cancer Center study.

Amonafide (nafidimide), a synthetic organic compound with an inhibitory effect on cellular replication, was used in a phase II study conducted by the Illinois Cancer Center in order to assess its efficacy and toxicity in advanced or recurrent squamous cell cancer of the head and neck. Eligible patients had received no more than one prior adjuvant or neoadjuvant chemotherapy, had normal bone marrow, renal and hepatic function, ECOG performance status of 0-2, and bidimensionally measurable disease. Eligible patients were administered amonafide at a starting dose of 300 mg/m2 for five consecutive days every 3 weeks with dose escalation or de-escalation according to established hematologic criteria in the absence of disease progression. Nineteen of 22 entered patients were evaluable for response and all patients were evaluable for toxicity. Eleven of 19 patients achieved stable disease. Median time to progression after start of treatment was 57 days, for the 18 patients for whom the date of progression is known. There were no partial or complete responses. Hematologic toxicity was dose limiting with grade 3-4 neutropenia in 50 percent of patients and 4 deaths associated with neutropenic sepsis. Non-hematologic toxicity was mild to moderate with nausea and vomiting predominating. In this study, amonafide was a myelotoxic, inactive treatment in advanced/recurrent head and neck cancer. Further use in head and neck cancer appears unwarranted.

Phase II study of fludarabine phosphate for gastric adenocarcinoma. An Illinois Cancer Center trial.

In an Illinois Cancer Center phase II trial, fludarabine phosphate was administered to a total of 14 patients (9 men, 5 women) with advanced, measurable, gastric adenocarcinoma. Fludarabine phosphate was given as a rapid intravenous (IV) bolus at a starting dose of 20 mg/m2/d for the first 5 days of a 28-day cycle. For subsequent cycles, the dose was escalated in increments of 2 mg/m2/d, provided that no toxicities greater than grade 1 were noted. In cases of grade 3 toxicity, dose reductions of 2 mg/m2/d were required, and patients who experienced grade 4 toxicities were removed from study. Receiving one complete 5-day course of fludarabine phosphate and surviving for 4 weeks on study were required for a patient to be evaluable for response. None of the patients responded to treatment. Although fludarabine phosphate was ineffective against gastric adenocarcinoma in this study, toxicity was acceptable at the 20 mg/m2/d times 5 every 28 days dose and schedule.

Phase II study of amonafide in gastric adenocarcinoma. An Illinois Cancer Center trial.

Twelve patients with recurrent, metastatic, or inoperable gastric adenocarcinoma were enrolled in an Illinois Cancer Center phase II trial of amonafide (nafidimide), a novel compound that acts as a DNA intercalator. Treatment consisted of a 60-minute infusion of amonafide which was administered daily for 5 consecutive days every 3 weeks at a starting dose of 300 mg/m2/d. Doses were modified according to the grade of toxicity experienced and eight patients underwent dose escalations. All 12 patients were evaluable for response and toxicities were predominantly hematologic. Stabilization of disease for at least 28 days was observed in seven patients and disease progression was noted in five. The median survival was 7.4 months. Doses were sufficient to produce severe bone marrow toxicity in one-third of the patients treated. None of the patients responded to therapy, implying a true response rate less than .221. Based on the results of this study, amonafide showed no activity against gastric adenocarcinoma; however toxicity appeared acceptable at the 300 mg/m2/d x 5 consecutive days every 3 weeks dose and schedule.

Phase II trial of fludarabine phosphate for adenocarcinoma of the pancreas. An Illinois Cancer Center study.

We have conducted a phase II trial of fludarabine phosphate for advanced measurable adenocarcinoma of the pancreas. The drug was administered every 4 weeks by a daily-times-5 bolus schedule beginning at 20 mg/m2/day. No responses were observed in 20 evaluable patients, 18 of whom were previously untreated. Dose-limiting toxicity was leukopenia, and gastroenterologic side effects were frequent. Life-threatening or fatal renal dysfunction occurred in 3 patients. In this schedule fludarabine phosphate is ineffective against adenocarcinoma of the pancreas and appears to have unpredictable severe renal toxicity.

Phase II trial of Bisantrene for metastatic melanoma: an Illinois cancer council study.

Sixteen patients with metastatic melanoma entered this phase II study of the efficacy of monthly cycles of Bisantrene. Toxicity was characterized by leukopenia, resulting in the hospitalization of one patient for a febrile incident, and superficial phlebitis. The results were similar to those of previous studies, in that among the 13 patients evaluable for response (six previously untreated with chemotherapy) there were no responses.

Phase II trial of 4' deoxydoxorubicin (DXDX) for unresectable non-small cell bronchogenic carcinoma. An Illinois Cancer Council study.

A phase II trial of 4' Deoxydoxorubicin (DXDX) was conducted in unresectable previously untreated non-small cell lung cancer patients. DXDX was administered every 3 weeks by short intravenous infusion at a starting dose of 30 mg/m2, with dose escalation to 40 mg/m2 toxicity permitting. Four responses, all partial, were observed in 35 evaluable patients, for a response rate of 11% (95% confidence limits 3.2% and 26.7%). Myelosuppression was the dose-limiting toxicity. Cardiotoxicity was not seen. DXDX has minimal activity against non-small cell lung cancer as a single agent at the dosage used in this study.

Phase II trial of fludarabine phosphate in advanced renal cell carcinoma: an Illinois Cancer Council Study.

Fludarabine Phosphate (FP), the 2-fluoro, 5'phosphate derivative of adenosine arabinoside (ara-A), was studied in 18 patients with advanced renal cell carcinoma. These patients had measurable disease and had not received chemotherapy. FP was administered at a loading dose of 20 mg/m2 followed by a 48-hour infusion at 30 mg/m2/day given every 21 days. There were no complete or partial responses seen. Toxicity was mainly hematologic, with leukopenia most commonly observed. FP given in this manner had no activity in advanced renal cell carcinoma.

Rapid and sensitive quantitative immunoassay for the large simian virus 40 T antigen.

A quantitative, enzyme-linked immunoadsorbent assay has been developed for the simian virus 40 large T antigen. When hamster anti-simian virus 40 tumor serum was used, this method permitted specific identification of large T antigen and its analog, the D2 hybrid protein, a molecule with the same C-terminal approximately 600 amino acids as large T antigen. The sensitivity limit of this test was 0.63 ng of protein. The slopes of the regression lines of the enzyme-linked immunosorbent assay titrations performed with highly purified D2 or simian virus 40 large T antigen and with crude extracts of simian virus 40-infected monkey and transformed human cells were identical. Thus, the curve generated with a purified protein, such as D2, can serve as a quantitative standard for the measurement of large T antigen in a wide variety of extracts. Furthermore, solutions containing high salt concentrations and buffers containing up to 0.1% Nonidet P-40 did not interfere with the assay, making it applicable to the measurement of large T antigen in a variety of chromatographic fractions. The enzyme-linked immunosorbent assay was three times more sensitive, was significantly faster to perform, and was quantitatively valid over a much broader large-T-antigen concentration range than the complement fixation test. As such, it should be useful in future studies of the structure and function of this protein.

Nucleotide-induced inhibition of surface sialyl transferase activity on cultured Burkitt's lymphoma cells.

Sialyl transferase activity was demonstrated on the surfaces of intact, cultured lymphoblastoid cells (RAJI) derived from a Burkitt's lymphoma. Pretreatment of the cells with neuraminidase increased the labeled sialoprotein by severalfold. A nunber of nucleotides were effective in decreasing the amount of sialoprotein assembly. CMP was the most effective inhibitor. UMP, AMP, and GMP were also inhibitory, but to a lesser degree. The diphosphate derivatives were similarly inhibitory, but generally less active than their monophosphate counterparts. The cyclic nucleotides were the least effective of all nucleotides tested; cCMP and cAMP showed a small degree of activity, whereas cUMP and cGMP were without effect. These studies indicated that a number of noncyclic and cyclic nucleotides can influence the activity of the sialyl transferase system.

Ganglioneuroblastoma in adults.

Ganglioneuroblastoma is a rare neoplasm of adults. Some information about the natural history and response to therapy can be obtained from two cases seen recently at our hospital and 17 cases in the literature. These tumors occur in adults of any age and are usually located in the retroperitoneum, mediastinum, or neck. Evidence of the tumor may be present years before diagnosis. Elevations of urinary catecholamines were documented in three cases and the levels correlated with progression or resection of the neoplasm. The tumor spreads either by local invasion or distant metastasis. Attempts at radiotherapy and chemotherapy in the treatment of unresectable or disseminated tumor has not resulted in objective improvement. This contrasts with the widely reported objective successes and cures of ganglioneuroblastomas occurring in childhood. Surgical excision of localized disease was the only curative therapeutic modality in the cases we reviewed.