Phase II trials of 5-day vinblastine infusion (NSC 49842), L-alanosine (NSC 153353), acivicin (NSC 163501), and aminothiadiazole (NSC 4728) in patients with recurrent or metastatic renal cell carcinoma

Abstract

One hundred and forty-four evaluable patients with recurrent or metastatic renal cell carcinoma (RCC) were treated with vinblastine infusion (n = 35), L-alanosine (n = 36), acivicin (n = 27), or aminothiadiazole (n = 46). Observed objective response rates of 9%, 3%, 4%, and 2%, respectively indicate that noe of these agents has significant antineoplastic activity in recurrent or metastatic RCC. Multivariate analysis of survival data suggests that initial performance status, time from initial diagnosis to study entry, and the presence or absence of lung metastases are important prognostic factors for survival. After adjustment for these factors, treatment assignment was also seen to be of prognostic value. All four treatments were generally well tolerated. There were no reports of life-threatening or lethal toxicities; however, 37% of the patients experienced severe reactions to treatment, primarily myelosuppression, anemia, neuropathies, and mucositis.

A Phase I/II Study of Infusional Vinblastine with the P-Glycoprotein Antagonist Valspodar (PSC 833) in Renal Cell Carcinoma

“…The maximum-tolerated dose (MTD) identified for infusional vinblastine in combination with oral valspodar was 0.6 mg/m 2 /d for 5 days, for a total dose of 3 mg/m 2 /cycle. This is approximately one-third of the 8.5 mg/m 2 /cycle (1.7 mg/m 2 /d for 5 days) vinblastine dose that can be administered to patients receiving infusional vinblastine for 5 days without a Pgp antagonist (14).…”

Acivicin Induces Apoptosis Independently of γ-Glutamyltranspeptidase Activity

“…It inhibits the growth of human pancreatic carcinoma cell line (MIA PaCa-2) and in vivo the growth of human breast and lung tumor xenografts in athymic mice. In phase I and II trials, acivicin has shown some benefits in the treatment of several solid tumor types (2,6).…”

Failure of Cytotoxic Chemotherapy, 1983–1988, and the Emerging Role of Monoclonal Antibodies for Renal Cancer

“…Other alkylating agents evaluated during the past 6 years in cluded a derivative of razoxane (ICRF-187; 135758), diaziquone (AZQ; 182986), dibromodulcitol or mitolactol (DBD; 04800), carboplatin (CBDCA; 241240), a tri epoxide alkalating agent 1,2,4-triglycidylurazol (TGU; 332488), and a new nitrosourea, a chlorethyl piperidyl derivative (PCNU; 95466). PCNU, 75-100 mg/m2 Q6W induced 1 remission in 79 patients [36,46] A glutamine antagonist from Streptomyces sviceus, acivicin (AT-125; 163501), was administered by contin uous intravenous infusion in a dose of 20 mg/m2/day for 3 consecutive days Q3W [5], The response rate was 4% in 27 cases. Another antitumor antibiotic from Strepto myces alanosinicus, alanosine (L-ALANO; 153353), was given to 36 patients in a dose of 160 mg/m2/day Q4W with 3% responding [5].…”

“…PCNU, 75-100 mg/m2 Q6W induced 1 remission in 79 patients [36,46] A glutamine antagonist from Streptomyces sviceus, acivicin (AT-125; 163501), was administered by contin uous intravenous infusion in a dose of 20 mg/m2/day for 3 consecutive days Q3W [5], The response rate was 4% in 27 cases. Another antitumor antibiotic from Strepto myces alanosinicus, alanosine (L-ALANO; 153353), was given to 36 patients in a dose of 160 mg/m2/day Q4W with 3% responding [5].…”

“…A purine derivative of adenosine arabinoside which is relatively resistant to deamination, fludarabine phosphate (2-FLAMP; 312887), was inactive in 45 pa tients [60,61]. Aminothiadiazole (A-TDA; 4728), a pu rine inhibitor of inosine monophosphate dehydrogenase, was administered to 46 patients, of whom 2% responded [5], and 5-aza-2-deoxycytidine (DAC; 127716), 75 mg every 8h Q5W, induced no response in 12 cases [62]. Lastly, doxifluridine (FUDR; 27640), an old agent used primarily for intrahepatic artery infusional therapy of colorectal carcinoma, was examined in a chronobiological schedule using a 14-day continuous infusion of 0.25 mg/kg/day with 68% of the daily dose administered between 1500 and 2100 h [63].…”