Lary J. Kilton

A phase II study of continuous infusion 5‐fluorouracil in advanced hormone refractory prostate cancer: An Illinois cancer center study

Background. 5‐Fluorouracil (5‐FU) has been previously associated with therapeutic benefit in hormone refractory prostate cancer. However, no previous study has administered 5‐FU as a prolonged continuous infusion, which may be the optimal schedule for this cell‐cycle specific agent.

A phase II clinical trial of echinomycin in metastatic soft tissue sarcoma - An Illinois cancer center study

SummaryEchinomycin, a cyclic peptide in the family of quinoxaline antibiotics, was evaluated in patients 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 × 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 trial of fludarabine phosphate for adenocarcinoma of the pancreas : an Illinois cancer center study

SummaryWe 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/m2day. 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 fludarabine phosphate in advanced renal cell carcinoma: An Illinois Cancer Council study

SummaryFludarabine 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.

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

SummaryAmonafide (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 amonafide in gastric adenocarcinoma : an Illinois cancer center trial

SummaryTwelve 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 echinomycin in advanced hormone-resistant prostate cancer : an Illinois cancer council study

Daniel H. Shevrin 1, Thomas E. Lad 2, Patrick Guinan 3, Lary J. Kilton 4, Alice Greenburg 5, Patricia Johnson 6, Richard R. Blough 7 and Holly Hoyer 7 1Evanston Hospital, Evanston, 1L; 2University of Illinois Hospital, Chicago, IL; SCook County Hospital, Chicago, IL; 4private practice, Barrington, IL; 5Decatur Memorial Hospital, Decatur, [L; 6Carle Clinic, Urbana, IL; 7Illinois Cancer Council, Chicago, IL, USA

High-dose aminothiadiazole in advanced colorectal cancer - An Illinois Cancer Center phase II trial

SummaryThirty-three patients with advanced colorectal carcinoma were entered on a phase II trial of weekly IV aminothiadiazole (175 mg/m2 escalated to 200 mg/m2) with concomitant allopurinol and non-steroidal anti-inflammatory agents (NSAIDs). Toxicity was predominantly GI, cutaneous, and chest pain/dyspnea. Twenty-five percent of patients had grade 3 or 4 toxicity. There were no responses in 27 evaluable patients. Median survival was 12 months. Aminothiadiazole, at higher doses than used in previous reports, when given with NSAIDs, had no significant activity against large bowel cancer.

Phase II trial of 6-thioguanine in advanced renal cell carcinoma - An Illinois Cancer Center study

Daniel H. Shevrin l, Lary J. Kilton 2, Thomas E. Lad 3, Michael Mullane 4, Ben Esparaz 5, Richard Knop 6, James Egner 7, Patricia Johnson 7, Richard Blough 8 , Suzanne French 8 and AI B. Benson, III 8 1Evanston Hospital, Evanston, IL; 2Private practice, Barrington, IL; 3 West Side Veterans Hospital, Chicago, IL; 4University of Illinois Hospital, Chicago, IL; 5Decatur Memorial Hospital, Decatur, IL; 6Glenbrook Hospital, Glenview, IL; 7Carle Clinic, Urbana, IL; 8Illinois Cancer Center, Chicago, IL, USA

Phase II trial of 4′ deoxydoxorubicin (DXDX) for unresectable non-small cell bronchogenic carcinoma

SummaryA 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.