Abstract:
OBJECTIVE:Poly(ADP-ribosyl) polymerases (PARPs) are nuclear enzymes with roles in DNA damage recognition and repair. PARP1 inhibition enhances the effects of DNA-damaging agents like doxorubicin. We sought to determine the recommended phase two dose (RP2D) of veliparib with pegylated liposomal doxorubicin (PLD) in breast and recurrent gynecologic cancer patients. METHODS:Veliparib and PLD were administered in a standard phase 1, 3 + 3 dose-escalation design starting at 50 mg veliparib BID on days 1-14 with PLD 40 mg/mg2 on day 1 of a 28-day cycle. Dose escalation proceeded in two strata: A (prior PLD exposure) and B (no prior PLD exposure). Patients underwent limited pharmacokinetic (PK) sampling; an expansion PK cohort was added. RESULTS:44 patients with recurrent ovarian or triple negative breast cancer were enrolled. Median age 56 years; 23 patients BRCA mutation carriers; median prior regimens four. Patients received a median of four cycles of veliparib/PLD. Grade 3/4 toxicities were observed in 10% of patients. Antitumor activity was observed in both sporadic and BRCA-deficient cancers. Two BRCA mutation carriers had complete responses. Two BRCA patients developed oral squamous cell cancers after completing this regimen. PLD exposure was observed to be higher when veliparib doses were > 200 mg BID. CONCLUSIONS:The RP2D is 200 mg veliparib BID on days 1-14 with 40 mg/m2 PLD on day 1 of a 28-day cycle. Anti-tumor activity was seen in both strata. However, given development of long-term squamous cell cancers and the PK interaction observed, efforts should focus on other targeted combinations to improve efficacy.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Pothuri B,Brodsky AL,Sparano JA,Blank SV,Kim M,Hershman DL,Tiersten A,Kiesel BF,Beumer JH,Liebes L,Muggia Fdoi
10.1007/s00280-020-04030-2subject
Has Abstractpub_date
2020-04-01 00:00:00pages
741-751issue
4eissn
0344-5704issn
1432-0843pii
10.1007/s00280-020-04030-2journal_volume
85pub_type
杂志文章,多中心研究abstract:BACKGROUND:Cediranib (RECENTIN™) is an oral, highly potent VEGF inhibitor. This study evaluated the effect of food on the pharmacokinetics of cediranib and compared the administration of continual cediranib via two dosing strategies using this as a platform to investigate pharmacodynamic imaging biomarkers. METHODS:Si...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s00280-010-1534-3
更新日期:2011-09-01 00:00:00
abstract:PURPOSE:Second-line chemotherapy in patients with metastatic gastric cancer (MGC) pre-treated with cisplatin is not a standard option. We studied a combination of irinotecan, fluorouracil and folates. METHODS:Patients progressive to cisplatin-based chemotherapy were enrolled. Irinotecan 180 mg/m(2), folinic acid 200 m...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0871-y
更新日期:2009-07-01 00:00:00
abstract:PURPOSE:Anti-angiogenic agents combined with histone deacetylase inhibitors act synergistically in vitro and in vivo. We conducted a phase I study of the combination of the anti-VEGF monoclonal antibody bevacizumab and histone deacetylase inhibitor valproic acid in patients with advanced cancers. METHODS:Bevacizumab w...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2384-1
更新日期:2014-03-01 00:00:00
abstract::There is no argument over using epidermal growth factor receptor (EGFR) mutation status to guide the frontline treatment for advanced lung adenocarcinoma (LADC); however, the role of the testing in lung squamous cell carcinoma (LSQC) remains controversial. Currently, the guidelines/consensus statements regarding EGFR ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-014-2536-3
更新日期:2014-10-01 00:00:00
abstract:PURPOSE:Gemcitabine (2',2'-difluorodeoxycytidine) is an antineoplastic agent with activity against a variety of solid tumors. To investigate its in vitro activity toward cervical cancer, we exposed six cervical cancer cell lines to gemcitabine. METHODS:Combinational cytotoxic studies using viability tests and clonogen...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800100370
更新日期:2001-12-01 00:00:00
abstract::Chemotherapy-induced intestinal damage is a very important dose-limiting side effect for which there is no definitive prophylaxis or treatment. This is in part due to the lack of understanding of its pathophysiology and impact on intestinal differentiation. The objective of this study was to investigate the gene expre...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0119-z
更新日期:2006-06-01 00:00:00
abstract::Seventy-three patients with Dukes' B2 and C colorectal cancer were randomized to adjuvant therapy after radical surgery. One group was treated with chemotherapy either alone or in combination with radiotherapy (RC). The second group was treated by chemotherapy (with or without radiotherapy) plus MER/BCG (RCM). In pati...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00292869
更新日期:1982-01-01 00:00:00
abstract::In five cancer patients we have determined the pharmacokinetics of 4'-deoxydoxorubicin (4'-DOX), its alcoholic metabolite 4'-deoxydoxorubicinol and the occurrence of circulating 7-deoxyaglycone metabolites. The 7-deoxyaglycone of the alcohol metabolite, the major aglycone of Adriamycin (ADR) present in man, was not de...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00570499
更新日期:1987-01-01 00:00:00
abstract:PURPOSE:The prognosis of gastroesophageal cancer is poor, and current regimens are associated with limited efficacy. The purpose of this study was to explore the safety and preliminary efficacy of docetaxel, oxaliplatin plus capecitabine for advanced cancer of the stomach or the gastroesophageal junction (GEJ). Seconda...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-015-2872-y
更新日期:2015-12-01 00:00:00
abstract:PURPOSE:To study the dual mechanism of action of FD137, a 3,3-disubstituted nitrosourea designed to block signaling mediated by the epidermal growth factor receptor (EGFR) on its own and to be hydrolyzed to an inhibitor of EGFR plus a DNA-damaging species. MATERIALS AND METHODS:HPLC was used to determine the half-life...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-002-0524-5
更新日期:2003-01-01 00:00:00
abstract:PURPOSE:To investigate the antitumor efficacy of pingyangmycin (PYM) in combination with anti-PD-1 antibody and determine the capability of PYM to induce immunogenic cell death (ICD) in cancer cells. METHODS:The murine 4T1 breast cancer and B16 melanoma models were used for evaluation of therapeutic efficacy of the co...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-020-04209-7
更新日期:2021-01-03 00:00:00
abstract::Advanced recurrent squamous cell head and neck cancer patients were prospectively randomized to receive or not receive dibromodulcitol 10 mg/kg PO weekly for 8 consecutive weeks in addition to bleomycin chemotherapy. Patients initially entered in the study received bleomycin 15 mu/m2 three times weekly for 8 weeks. Th...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00255478
更新日期:1982-01-01 00:00:00
abstract:PURPOSE:The blood-brain barrier discriminates the access of several molecules to the brain. This hampers the use of some drugs, as doxorubicin, potentially active for treatment of brain tumors. We explored the feasibility of active modification of the blood-brain barrier protection, by using morphine pretreatment, to a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1429-3
更新日期:2011-06-01 00:00:00
abstract::Acute promyelocytic leukemia (APL) is characterized by the expansion of malignant myeloid cells blocked at the promyelocytic stage of hemopoietic development and is invariably associated with reciprocal chromosomal translocations involving the retinoic acid receptor alpha (RARalpha) gene on chromosome 17. RARalpha var...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s002800100322
更新日期:2001-08-01 00:00:00
abstract::We obtained evidence that the cytotoxic effect of 5-fluorouracil (5-FU) is augmented when the drug is given in combination with hyperthermia (HYP) and dipyridamole (DP). Nontoxic levels of DP enhanced the combined cytotoxicity of 5-FU and HYP against B16 melanoma and human tumor cells in vitro as measured by the succi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685941
更新日期:1992-01-01 00:00:00
abstract::Carboxypeptidase G2 (CPG2) is used when unexpected toxicity or renal failure occurs during high-dose methotrexate therapy. Leucovorin is also administered to antagonise the effects of methotrexate on purine anabolism. To investigate the effects of CPG2 on leucovorin rescue, we incubated the enzyme with both stereoisom...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0910-2
更新日期:2005-04-01 00:00:00
abstract:BACKGROUND:TAP chemotherapy (paclitaxel, doxorubicin, and cisplatin) is effective for advanced and recurrent endometrial carcinoma, but has occasional severe toxicity. TEC chemotherapy (paclitaxel, epirubicin, and carboplatin) has been suggested to have less toxicity; however, the optimal dosage has yet to be determine...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1638-4
更新日期:2011-12-01 00:00:00
abstract:PURPOSE:The study was undertaken to determine the metabolism of dexrazoxane (ICRF-187) to its one-ring open hydrolysis products and its two-rings opened metal-chelating product ADR-925 in cancer patients with brain metastases treated with high-dose etoposide. In this phase I/II trial dexrazoxane was used as a rescue ag...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-003-0619-7
更新日期:2003-08-01 00:00:00
abstract:BACKGROUND AND AIMS:oxaliplatin in combination with folinic acid (FA) and infusional 5-fluorouracil (5-FU) has shown significant anti-tumor activity in gastric cancer patients (FOLFOX). Previous studies have shown that gemcitabine (GEM), a new fluorinated anti-metabolite, enhances the individual anti-tumor activity of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-005-1024-1
更新日期:2005-12-01 00:00:00
abstract:PURPOSE:To determine the safety, the maximal tolerated dose, and to assess for any clinical activity of pomalidomide given to patients with advanced solid tumors. PATIENTS AND METHODS:Patients with incurable solid tumors were enrolled. Two different dosing schedules were explored. In Cohort A patients were given pomal...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-1919-6
更新日期:2012-11-01 00:00:00
abstract:PURPOSE:miRNAs are implicated in drug resistance of multiple cancers including non-small cell lung cancer (NSCLC), highlighting the potential of miRNAs as chemoresistance regulators in cancer treatment. This study aims to explore the relationship between miR-181c and chemoresistance of NSCLC cells. METHODS:qRT-PCR was...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-017-3435-1
更新日期:2017-11-01 00:00:00
abstract::Human plasma was incubated with cisplatin over 24 h. Ultrafilterable platinum and platinum reactive with DDTC were determined at regular time intervals during incubation. At each time point more platinum reacted with sodium N,N1-diethyldithiocarbamate (DDTC) than was available as ultrafilterable platinum. At 24 h 70% ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00570487
更新日期:1987-01-01 00:00:00
abstract:PURPOSE:D-Limonene is a natural monoterpene with pronounced chemotherapeutic activity and minimal toxicity in preclinical studies. A phase I clinical trial to assess toxicity, the maximum tolerated dose (MTD) and pharmacokinetics in patients with advanced cancer was followed by a limited phase II evaluation in breast c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800050793
更新日期:1998-01-01 00:00:00
abstract:PURPOSE:In order to determine the sensitivity and specificity of the test and to optimize experimental conditions utilizing the SBT in a rat model of chemotherapy-induced small intestinal damage. METHODS:Initially, a 13C-sucrose dose-response study was performed in rats to determine an optimal sucrose concentration fo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1098-2
更新日期:2010-04-01 00:00:00
abstract:PURPOSE:Busulfan (Bu) exposure is critical for efficacy and safety. Body weight (BW), or adjusted ideal body weight (AIBW)-based dosing (WBD) algorithm, has been used in hematopoietic stem cell transplantation (HSCT). A recently completed phase 2 study revealed that 33.6 % of the subjects were under-, or over-exposed, ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-014-2660-0
更新日期:2015-03-01 00:00:00
abstract:BACKGROUND:Pre-clinical activity of SSG against melanoma and renal cancer has been identified recently although the drug's mechanism of action and activity against tumors of additional histological-types remain undefined. METHODS:The effects of SSG and SSG combination with other agents on DU145 human prostate carcinom...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0378-3
更新日期:2007-08-01 00:00:00
abstract:PURPOSE:Leucovorin is commonly used as folate supplement in 5-fluorouracil-based chemotherapy, but needs to be converted to active 5,10-methylenetetrahydrofolate (methyleneTHF) intracellularly. This provides for interindividual differences. MethyleneTHF has recently been developed into the stable, distributable drug, M...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00280-014-2611-9
更新日期:2015-01-01 00:00:00
abstract::The interactions of cisplatin, 5-fluorouracil, doxorubicin, mitomycin, carmustine (BCNU), cyclophosphamide, methotrexate and thio-TEPA were assessed at three neurotransmitter receptor binding sites. Each drug was inactive at concentrations as high as 10(-4) M in displacing the specific binding of 3H-spiperone to dopam...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254564
更新日期:1987-01-01 00:00:00
abstract:PURPOSE:Mutations and activations of the MEK and PI3K pathways are associated with the development of many cancers. GDC-0973 and GDC-0941 are inhibitors of MEK and PI3K, respectively, currently being evaluated clinically in combination as anti-cancer treatment. The objective of these studies was to characterize the rel...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-012-1988-6
更新日期:2013-01-01 00:00:00
abstract::To determine whether dimethylsulfoxide (DMSO) can potentiate antitumor activity of cyclophosphamide (CYC) in patients with squamous cell carcinoma of the lung, 14 patients were treated with 5 l of a 5% or 6% DMSO solution PO over 3 days and 1,500 mg CYC/m2 IV as a 60-min infusion on the third day of treatment. Serial ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00262327
更新日期:1981-01-01 00:00:00