abstract：PURPOSE:Pyrazoloacridine (PZA) is an acridine derivative selected for clinical development because of broad pre-clinical antitumor activity and solid tumor selectivity. Phase I evaluations with PZA have demonstrated predictable toxicity and suggested clinical efficacy. A phase II trial in patients with previously untre...

journal_title：Investigational new drugs

authors： Zalupski MM,Shields AF,Philip PA,Kraut M,LoRusso P,Heilbrun LK,Vaitkevicius V

更新日期：1998-01-01 00:00:00

abstract：:Gemcitabine (GEM) is a novel nucleoside analogue with a unique mechanism of action. Preliminary studies have shown a mild, schedule-dependent toxic profile with a broad range of MTDs and promising antitumor activity in various solid tumors. This phase I study describes the infusion length-effect relationships of low- ...

journal_title：Investigational new drugs

authors： Pollera CF,Ceribelli A,Crecco M,Oliva C,Calabresi F

更新日期：1997-01-01 00:00:00

abstract：:The matrix metalloproteinases (MMPs) are a family of at least fifteen secreted and membrane-bound zinc-endopeptidases. Collectively, these enzymes can degrade all of the components of the extracellular matrix, including fibrallar and non-fibrallar collagens, fibronectin, laminin and basement membrane glycoproteins. MM...

journal_title：Investigational new drugs

authors： Wojtowicz-Praga SM,Dickson RB,Hawkins MJ

更新日期：1997-01-01 00:00:00

abstract：:Interleukin-4 (IL-4) is a pleiotropic cytokine affecting growth and differentiation of various cell types as well as regulating other cytokines. To study the effect of IL-4 on AIDS-related Kaposi's sarcoma (AIDS-KS) cells, we first examined the tumor cells for IL-4 receptor (IL-4R) expression. KS cells express a singl...

journal_title：Investigational new drugs

authors： Cai J,Zheng T,Murphy J,Waters CA,Lin GY,Gill PS

更新日期：1997-01-01 00:00:00

abstract：:Androgen receptors are present in both pancreatic cancer tissue and cell lines. Flutamide is a potent antiandrogen widely used in clinical practice for patients with metastatic prostate cancer. This Phase II trial was undertaken to evaluate the impact of flutamide in patients with advanced pancreatic adenocarcinoma wh...

journal_title：Investigational new drugs

authors： Sharma JJ,Razvillas B,Stephens CD,Hilsenbeck SG,Sharma A,Rothenberg ML

更新日期：1997-01-01 00:00:00

abstract：:Matrix metalloproteinases (MMPs) are a class of structurally related enzymes that function in the degradation of extracellular matrix proteins that constitute the pericellular connective tissue and play an important role in both normal and pathological tissue remodelling. Increased MMP activity is detected in a wide r...

journal_title：Investigational new drugs

authors： Denis LJ,Verweij J

更新日期：1997-01-01 00:00:00

abstract：:Topotecan (NSC 609099) is a camptothecin analogue that demonstrated activity against a variety of human tumors in preclinical studies. A phase II trial was performed with topotecan given to patients with locally advanced or metastatic adenocarcinoma of the stomach. Topotecan was administered IV Bolus over 30 minutes o...

journal_title：Investigational new drugs

authors： Benedetti JK,Burris HA 3rd,Balcerzak SP,Macdonald JS

更新日期：1997-01-01 00:00:00

abstract：:Gemcitabine is a nucleoside analogue with excellent clinical activity against solid tumors. Within the cell, gemcitabine is rapidly phosphorylated to its active di- and triphosphate metabolites. Cytotoxicity with gemcitabine appears to be related to multiple effects on DNA replication, where gemcitabine triphosphate c...

journal_title：Investigational new drugs

authors： Shewach DS,Lawrence TS

更新日期：1996-01-01 00:00:00

abstract：:The current recommendations for Phase I trials should allow more confident interpretation of the toxicity and efficacy of new agents by providing a framework for multicentre and international co-operation. An overview of the aims and designs of Phase I trials is presented, along with a summary of current and recently ...

journal_title：Investigational new drugs

authors： Estlin EJ,Ablett S,Newell DR,Lewis IJ,Lashford L,Pearson AD

更新日期：1996-01-01 00:00:00

abstract：:A new anthracycline derivative, SM5887, in combination with commonly used anticancer agents was evaluated against T-cell leukemia MOLT-3 and human osteosarcoma MG-63 cell lines in culture. MOLT-3 and MG-63 cells were incubated with various concentrations of 13-hydroxy SM5887 (SM5887-OH, the active metabolite of SM5887...

journal_title：Investigational new drugs

authors： Takagi T,Yazawa Y,Suzuki K,Yamauchi Y,Kano Y

更新日期：1996-01-01 00:00:00

abstract：:N-(phosphonacetyl)-disodium L-aspartic acid (PALA) demonstrates a synergistic antitumor effect when combined with 5-Fluorouracil (5-FU) in in vitro studies. In a Phase II trial, 23 eligible patients with unresectable or metastatic adenocarcinoma of the stomach were treated with weekly i.v. bolus PALA (250 mg/M2) follo...

journal_title：Investigational new drugs

authors： Martino RL,Fleming TR,Morrell LM,Ardalan B,Richman SP,Macdonald JS

更新日期：1996-01-01 00:00:00

abstract：:CC-1065 is a unique alkylating agent that preferentially binds in the minor groove of double-stranded DNA at adenine-thymine-rich sites. Although it has broad antitumor activity in preclinical models its development was discontinued because of deaths observed during preclinical toxicology studies. Adozelesin is a pote...

journal_title：Investigational new drugs

authors： Foster BJ,LoRusso PM,Poplin E,Zalupski M,Valdivieso M,Wozniak A,Flaherty L,Kasunic DA,Earhart RH,Baker LH

更新日期：1996-01-01 00:00:00

abstract：:Degradation of basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be required for tumor invasion, tumor-induced angiogenesis and vascular invasion. A synthetic hydroxamate, batimastat (also known as BB-94), inhibits MMPs by binding the zinc ion in the active site of the MMP. ...

journal_title：Investigational new drugs

authors： Wojtowicz-Praga S,Low J,Marshall J,Ness E,Dickson R,Barter J,Sale M,McCann P,Moore J,Cole A,Hawkins MJ

更新日期：1996-01-01 00:00:00

abstract：:Taxol was administered as a 24-hour continuous infusion at 250 mg/m2 in this Phase II trial in patients with adenocarcinomas of the upper gastrointestinal tract (UGIT). Twenty-five patients were entered between July 1991 and June 1992, twenty-three were eligible and were evaluated for toxicity and twenty-two were asse...

journal_title：Investigational new drugs

authors： Einzig AI,Lipsitz S,Wiernik PH,Benson AB 3rd

更新日期：1995-01-01 00:00:00

abstract：:Fifteen patients with advanced, cisplatin-refractory germ cell tumors (GCT) were treated on a phase II trial with topotecan. None of the 14 evaluable patients achieved a complete or partial response. Myelosuppression was the major toxicity. The median nadir leukocyte count was 1.75 cells/mm3, neutrophil count was 1.55...

journal_title：Investigational new drugs

authors： Puc HS,Bajorin DF,Bosl GJ,Amsterdam A,Motzer RJ

更新日期：1995-01-01 00:00:00

abstract：:The diarylsulfonylureas have shown promise in xenograft models of childhood cancer. Sulofenur has been evaluated in phase I and II trials in adults with a variety of solid tumors, but the toxicity and maximum tolerated dose of sulofenur in children and adolescents have not been determined. In a phase I study, sulofenu...

journal_title：Investigational new drugs

authors： Pratt CB,Bowman LC,Marina N,Pappo A,Avery L,Luo X,Meyer WH

更新日期：1995-01-01 00:00:00

abstract：PURPOSE:To evaluate the response to oral Etoposide when combined with mesna, ifosfamide, and mitoxantrone in patients with relapsed and/or refractory lymphoma. To evaluate response and its duration after administration of intravenous Etoposide, methylprednisolone, high-dose cytosine arabinoside, and cisplatin (ESHAP) a...

journal_title：Investigational new drugs

authors： Romaguera JE,Rodriguez MA,Hagemeister FB,McLaughlin P,Swan F,Moore DF Jr,Sarris AH,Younes A,Hill D,Cabanillas F

更新日期：1994-01-01 00:00:00

abstract：:Bryostatin 1 (Bryo) is a naturally occurring macrocyclic lactone with antineoplastic activity. Like the phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) it directly activates the calcium- and phospholipid-dependent protein kinase C (PKC), thus generating a number of different cellular responses. We investigat...

journal_title：Investigational new drugs

authors： Steube KG,Grunicke D,Drexler HG

更新日期：1994-01-01 00:00:00

abstract：:Menogaril, a semisynthetic anthracycline antibiotic, was administered to patients with metastatic adenocarcinoma of the prostate. Forty-five patients with measurable disease and 45 patients with evaluable disease received 150-200 mg/m2 over 1 hour every 28 days. There were three partial responses (PR) among 87 patient...

journal_title：Investigational new drugs

authors： Taylor SA,Blumenstein BA,Stephens RL,Crawford ED,Pistone B,Hill JB

更新日期：1994-01-01 00:00:00

abstract：:Thirty-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 (NSAID's). Toxicity was predominantly GI, cutaneous, and chest pain/dyspnea. Twenty-five per...

journal_title：Investigational new drugs

authors： Locker GY,Kilton L,Khandekar JD,Lad TE,Knop RH,Albain K,Blough R,French S,Benson AB 3rd

更新日期：1994-01-01 00:00:00

abstract：BACKGROUND:Relatively few studies have examined the activity of alkylating agents in the treatment of advanced colorectal adenocarcinoma. Recent reports have suggested possible therapeutic activity for high-dose intravenous melphalan administered with autologous bone marrow transplantation (BMT) support. We conducted a...

journal_title：Investigational new drugs

authors： Moore DF Jr,Pazdur R,Abbruzzese JL

更新日期：1994-01-01 00:00:00

abstract：:Diflubenzuron (DFB) and Clanfenur (CFN) belong to a group of compounds called Benzoylphenyl Ureas (BPUs). Several BPUs regulate cell growth in insects and/or inhibit growth of B-16 murine melanomas. In view of potential clinical use for these compounds, DFB and CFN were selected as examples of BPUs and tested for effe...

journal_title：Investigational new drugs

authors： Jenkins VK,Juneja HS,Ives K,Lee S,Perry RR

更新日期：1993-11-01 00:00:00

abstract：:A novel schedule of 5-fluorouracil administration has been developed for biochemical modulation studies. In combination with the pyrimidine synthesis inhibitor PALA, 5-fluorouracil has been given as a 24-hour infusion, repeated weekly: a dose of 2600 mg/m2 is well tolerated. To identify a suitable dose of 5-fluorourac...

journal_title：Investigational new drugs

authors： Haas NB,Hines JB,Hudes GR,Johnston N,Ozols RF,O'Dwyer PJ

更新日期：1993-05-01 00:00:00

abstract：:Chloroquinoxaline sulfonamide (CQS) has been developed to the clinical trial stage based on its activity in the Human Tumor Colony Forming Assay (HTCFA). In the HTCFA, CQS demonstrated inhibition of colony formation against breast, lung, melanoma and ovarian carcinomas. The mechanism of action of CQS is unknown. It do...

journal_title：Investigational new drugs

authors： Fisherman JS,Osborn BL,Chun HG,Plowman J,Smith AC,Christian MC,Zaharko DS,Shoemaker RH

更新日期：1993-02-01 00:00:00

abstract：:Pre-clinical and clinical studies have shown that trifluoperazine (TFP) can modulate multidrug resistance. We have performed a Phase II trial of TFP and doxorubicin in doxorubicin-naive patients with metastatic breast cancer. We hypothesized that TFP would inhibit the development of doxorubicin resistance, resulting i...

journal_title：Investigational new drugs

authors： Budd GT,Bukowski RM,Lichtin A,Bauer L,Van Kirk P,Ganapathi R

更新日期：1993-02-01 00:00:00

abstract：:Interleukin-4 is a highly pleiotropic T-cell derived lymphokine that has been reported to stimulate a host cell-mediated antitumor response. Recombinant human interleukin-4 (rhuIL-4) is currently undergoing clinical phase I trials. We have studied the growth modulating effects of rhuIL-4 on a variety of freshly explan...

journal_title：Investigational new drugs

authors： Hanauske AR,Degen D,Marshall MH,Trotta PP,Von Hoff DD

更新日期：1992-11-01 00:00:00

abstract：:Fifteen patients with advanced, cisplatin-refractory germ cell tumors (GCT) were treated with iproplatin (CHIP). No objective responses were noted in any of the patients treated. By restricting the entry criteria to heavily pre-treated patients, the identification of new active agents in phase II trials may be hindere...

journal_title：Investigational new drugs

authors： Murphy BA,Motzer RJ,Bosl GJ

更新日期：1992-11-01 00:00:00

abstract：:Mitonafide is the lead compound of a new series of antitumor drugs, the 3-Nitronaphthalimides, which have shown antineoplastic activity in vitro as well as in vivo. This phase I Mitonafide study in non-small cell lung cancer using a 120-hour continuous infusion (120 h. C.I.) schedule of administration was designed to ...

journal_title：Investigational new drugs

authors： Rosell R,Carles J,Abad A,Ribelles N,Barnadas A,Benavides A,Martin M

更新日期：1992-08-01 00:00:00

abstract：:Didemnin B is a depsipeptide derived from a Caribbean tunicate (sea squirt) that has demonstrated antineoplastic activity against a variety of murine tumor models, including the L1210 and P388 leukemia, the B16 melanoma, and M5076 sarcoma cell lines. Based on these data, we designed a phase II trial in which 15 patien...

journal_title：Investigational new drugs

authors： Jones DV Jr,Ajani JA,Blackburn R,Daugherty K,Levin B,Patt YZ,Abbruzzese JL

更新日期：1992-08-01 00:00:00

abstract：:Fifteen patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck received a 5 day continuous I.V. infusion of 6-thioguanine repeated every five weeks. Dose limiting toxicity was primarily hematological with grade III/IV leucopenia and thrombocytopenia seen in seven patients. Nausea and vo...

journal_title：Investigational new drugs

authors： Kruter F,Eisenberger M,Sinibaldi V,Engstrom C,Jacobs M,Abrams J,Belani C,Gray W,Krasnow S

更新日期：1992-07-01 00:00:00

abstract：:Seventeen patients with small cell lung cancer entered a phase II trial testing the feasibility of adding high dose epirubicin (100-120 mg/m2, day 1) in combination with etoposide (60-80 mg/m2, days 1-5) and cisplatin (70 mg/m2, day 1) courses repeated every three weeks. Complete responders received thoracic (40 Gy) a...

journal_title：Investigational new drugs

authors： Rosell R,Carles J,Abad A,Jimeno JM,Moreno I,Barnadas A,Ribelles N,Haboubi N

更新日期：1992-07-01 00:00:00

abstract：:A Phase II study of Didemnin-B, a marine cyclic depsipeptide, was undertaken in patients with progressive epithelial ovarian cancer. The starting dose was 2.6 mg/m2. Fifteen patients received the drug, of whom twelve were evaluable. There were no responses observed in the twelve patients. The two most frequent toxicit...

journal_title：Investigational new drugs

authors： Cain JM,Liu PY,Alberts DE,Gallion HH,Laufman L,O'Sullivan J,Weiss G,Bickers JN

更新日期：1992-04-01 00:00:00

abstract：:This report shows that N-acylation of the protein kinase C (PKC) substrate Arg-Lys-Arg-Thr-Leu-Arg-Arg-Leu (RKRTLRRL) provides it with a potent inhibitory activity against PKC. N-myristoyl-RKRTLRRL inhibited Ca2(+)- and phosphatidylserine (PS)-dependent histone phosphorylation catalyzed by PKC with a 50% inhibitory co...

journal_title：Investigational new drugs

authors： O'Brian CA,Ward NE,Liskamp RM,de Bont DB,Earnest LE,van Boom JH,Fan D

更新日期：1991-05-01 00:00:00

abstract：:AZQ was given intravenously to 23 patients with mixed mesodermal sarcoma of the uterus refractory to conventional treatment at a dose of 22.5-30 mg/m2 q three weeks. There was one partial response lasting seven weeks and one drug-related death. Based upon the activity observed in this trial, there does not appear to b...

journal_title：Investigational new drugs

authors： Slayton RE,Blessing JA,Clarke-Pearson D

更新日期：1991-02-01 00:00:00

abstract：:3-Deazaguanine (Dezaguanine), a purine antimetabolite, was evaluated in a phase I trial in 42 patients with advanced solid tumors. Dezaguanine was given as a weekly intravenous infusion for three consecutive weeks of a four-week cycle. The dose ranged from 30 to 2000 mg/m2; no consistent dose-limiting hematologic or g...

journal_title：Investigational new drugs

authors： Margolin K,Doroshow J,Leong L,Akman S,Carr B,Odujinrin O,Flanagan B,Grove W,DeLap R,Goldberg D

更新日期：1990-11-01 00:00:00

abstract：:Trimetrexate (TMTX) is an analog of methotrexate and a potent inhibitor of the enzyme dihydrofolate reductase. In this phase I study, TMTX was given intravenously to 32 patients as a constant infusion over 24 hours every 28 days. The maximum-tolerated dose of TMTX was 200 mg/m2, with myelosuppression as the dose-limit...

journal_title：Investigational new drugs

authors： Allegra CJ,Jenkins J,Weiss RB,Balis F,Drake JC,Brooks J,Thomas R,Curt GA

更新日期：1990-05-01 00:00:00

abstract：:Fifty-four evaluable patients with SCLC previously treated with chemotherapy received either N-methylformamide or spirogermanium. There was one partial response to N-methylformamide. The median survival times for patients treated with N-MF and spirogermanium were 11.7 and 12.6 weeks respectively. Five patients treated...

journal_title：Investigational new drugs

authors： Ettinger DS,Finkelstein DM,Abeloff MD,Chang YC,Smith TJ,Oken MM,Ruckdeschel JC

更新日期：1990-05-01 00:00:00

abstract：:A short-term antimetabolic assay based upon the inhibition of incorporation of nucleic acid precursors was used to compare the cytotoxicity of a new halogenated anthracycline, 4'-iodo-4'-deoxydoxorubicin (IDX), with that of its parent compound doxorubicin (DX) on human colo-rectal carcinoma specimens. IDX showed a mar...

journal_title：Investigational new drugs

authors： Villa R,Zaffaroni N,Giuliani F,Colella G,Sanfilippo O,Silvestrini R

更新日期：1990-05-01 00:00:00

abstract：: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, wer...

journal_title：Investigational new drugs

authors： Rose C,Lad TE,Kilton LJ,Schor J,Rosen ST,Rossof AH,Blough RR,Johnson CM

更新日期：1990-02-01 00:00:00

abstract：:In this multi-institutional phase II study, VM-26 or Teniposide was administered to forty-two patients with advanced colorectal cancer. Patients were initially treated at 60 mg/M2 daily for 5 days with dose adjustments depending on toxicity. One complete response and one partial response were observed lasting six and ...

journal_title：Investigational new drugs

authors： Oishi N,Fleming TR,Laufman L,Ungerleider JS,Natale RB,Einstein AB Jr,Von Hoff DD,Macdonald JS

更新日期：1990-02-01 00:00:00