Abstract:
:Background It would be useful to have criteria for predicting long-term treatment responses to immune checkpoint inhibitors (ICIs). Maximum depth of response correlates with treatment outcomes among patients receiving programmed death protein 1 axis inhibitors for non-small cell lung cancer (NSCLC). We investigated associations between early depth of response and survival outcomes among patients receiving nivolumab for NSCLC. Methods Using records from prospective observational cohorts, we identified 83 previously treated advanced patients with NSCLC who received nivolumab during 2016-2017. Thirty-one patients who achieved disease control were analyzed. Tumor assessments followed the Response Evaluation Criteria in Solid Tumors (RECIST). Using Kaplan-Meier and receiver operating characteristic (ROC) curve analyses, treatment outcomes were compared with percent tumor reductions from baseline to the first evaluation (8-12 weeks after starting nivolumab). Results Early depth of response was predictive of 6-month progression-free survival (area under the ROC curve, 0.848). Based on ROC results, early tumor shrinkage was defined as a > 10% reduction by the first evaluation. Early tumor shrinkage was associated with significantly longer median progression-free survival (early tumor shrinkage: 16.6 months, 95% confidence interval [CI] 8.5 months-not reached; no early shrinkage: 5.1 months, 95% CI 3.9-6.8 months; P < 0.001) and significantly longer median overall survival (P = 0.046). Conclusions Early depth of tumor shrinkage was associated with outcomes after ICI treatment. Because of its simplicity and predictive ability, early tumor shrinkage may be a promising factor for use in clinical settings. However, confirmation of our results is needed.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Kawachi H,Fujimoto D,Morimoto T,Hosoya K,Sato Y,Kogo M,Nagata K,Nakagawa A,Tachikawa R,Tomii Kdoi
10.1007/s10637-019-00770-ysubject
Has Abstractpub_date
2019-12-01 00:00:00pages
1257-1265issue
6eissn
0167-6997issn
1573-0646pii
10.1007/s10637-019-00770-yjournal_volume
37pub_type
杂志文章abstract:PURPOSE:Combining proteasome and histone deacetylase (HDAC) inhibition has been seen to provide synergistic anti-tumor activity, with complementary effects on a number of signaling pathways. The novel bi-cyclic structure of marizomib with its unique proteasome inhibition, toxicology and efficacy profiles, suggested uti...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9766-6
更新日期:2012-12-01 00:00:00
abstract::Ninhydrin (2,2-dihydroxy-1,3-indane dione) was evaluated for its antitumor and cytotoxic properties in Ehrlich ascites carcinoma cell (EAC Cell)-bearing mice. The rationale behind this study has been mainly the literature reports of its characteristic interference with DNA synthesis and calcium homeostasis. Antitumor ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1023/a:1006465504723
更新日期:2000-08-01 00:00:00
abstract::Studies with CGP 41 251 (I), an N-benzoylstaurosporine derivative and PKC-alpha inhibitor, revealed that oral administration of 400 microg/day of the compound to wild type mice on four successive days reversed multi drug resistance (Killion et al. Oncology Research 7: 453-459, 1995). In our study, the same regimen of ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1023/a:1006260217400
更新日期:1999-01-01 00:00:00
abstract:AIM:To quantify the effect of food on the systemic exposure of lapatinib at steady state when administered 1 h before and after meals, and to observe the safety and tolerability of lapatinib under these conditions in patients with advanced solid tumours. METHODS:This was a three-treatment, randomised, three-sequence c...
journal_title:Investigational new drugs
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10637-013-0055-4
更新日期:2014-06-01 00:00:00
abstract::Sphingosine-1-phosphate (S1P) is an important regulator of cancer development and progression. Its cellular concentration is controlled predominantly by sphingosine kinase (SK) and sphingosine-1-phosphate lyase (SPL). In the current study we showed that mRNA expressions for both SK and SPL were up-regulated throughout...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9375-9
更新日期:2011-04-01 00:00:00
abstract::Cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N(4)]-chloride platinum (II) monohydrochloride monohydrate (DPR) is a new platinum triamine complex obtained from the synthesis of cisplatin and procaine. In this paper we analyzed, adopting a disease-oriented strategy, the tumour selectivity of this compound...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1023/b:drug.0000006170.38419.c9
更新日期:2004-01-01 00:00:00
abstract::Apoptin is a nonstructural protein encoded by one of the three open reading frames of the chicken anemia virus genome. It has attracted a great deal of interest due to its ability to induce apoptosis in multiple transformed and malignant mammalian cell lines without affecting primary and non-transformed cells. However...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-017-0431-6
更新日期:2017-06-01 00:00:00
abstract::As HER2 is a client protein of the molecular chaperone Hsp90, targeting Hsp90 may be beneficial in HER2-positive breast cancer. In this study, the activity of the Hsp90 inhibitor NVP-AUY922 was assessed in HER2 overexpressing breast cancer cell lines, including two cell line models of acquired trastuzumab-resistance. ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-017-0556-7
更新日期:2018-08-01 00:00:00
abstract::To explore the clinical significance of the level of HER2/neu gene amplification in a homogenous cohort of 33 patients with HER2-positive metastatic breast cancer (MBC) and available tumor samples treated with a trastuzumab-based regimen, we retrospectively performed dual-color fluorescence in-situ hybridization test ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9155-y
更新日期:2009-04-01 00:00:00
abstract::Receptor tyrosine kinases (RTKs) modulate a variety of cellular events, including cell proliferation, differentiation, mobility and apoptosis. In addition, RTKs have been validated as targets for cancer therapies. Microtubules are another class of proven targets for many clinical anticancer drugs. Here, we report that...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9577-1
更新日期:2012-04-01 00:00:00
abstract:INTRODUCTION:Continuous efforts from scientists of diverse fields are necessary not only to better understand the mechanism by which multidrug resistant (MDR) cancer cells occur, but also to boost the discovery of new cytotoxic compounds. This work was designed to assess the cytotoxicity and the mechanism of action of ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-014-0137-y
更新日期:2014-12-01 00:00:00
abstract:PURPOSE:To assess the maximum well-tolerated dose (MWTD), dose limiting toxicity (DLT), pharmacokinetics (PK) and pharmacodynamics of zibotentan, a novel specific endothelin-A receptor antagonist, in patients with metastatic prostate cancer. METHODS:Patients with metastatic, castrate-resistant prostate cancer (CRPC) w...
journal_title:Investigational new drugs
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-009-9318-5
更新日期:2011-02-01 00:00:00
abstract:PURPOSE:To investigate the hypothesis that a systemic agent designed to inhibit dihydropyrimidine dehydrogenase (DPD), the first enzyme in the fluoropyrimidine degradative pathway, could improve the effective amount of 5-fluorouracil (5-FU) delivered to a tumor resulting in enhanced response. PATIENTS AND METHODS:Elig...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1023/a:1020662113061
更新日期:2002-11-01 00:00:00
abstract::4-demethoxydaunorubicin (4-dm DNR), a new analog of daunorubicin, was tested at an every 3-week dose schedule in 63 evaluable patients with various forms of disseminated malignancy. Utilizing the intravenous (i.v.) route of administration, the maximum tolerated dose (MTD) was 15-18 mg/m2; with the oral route the MTD w...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00172075
更新日期:1983-01-01 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
pub_type: 杂志文章
doi:10.1007/BF00944180
更新日期:1992-11-01 00:00:00
abstract:PURPOSE:DDB (dimethyl-4,4'-dimethoxy-5,6,5'6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate) is a synthetic hepatoprotectant which has been widely used to treat chronic viral hepatitis B patients in China for more than 20 years. In this study, we evaluated DDB as a multidrug resistance (MDR) chemosensitizing agent. MET...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-006-9001-z
更新日期:2007-04-01 00:00:00
abstract:BACKGROUND:Dacomitinib (PF-00299804) is an oral, irreversible, small molecule inhibitor of human epidermal growth factor receptor-1, -2, and -4 tyrosine kinases. METHODS:This phase I, open-label, dose-escalation study (clinicaltrials.gov: NCT00783328) primarily evaluated the safety and tolerability of dacomitinib by d...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9789-z
更新日期:2012-12-01 00:00:00
abstract::Background We determined the safety, pharmacokinetics, pharmacodynamics, and antitumour activity of abexinostat in B-cell lymphoma or chronic lymphocytic leukaemia. Patients and methods Thirty-five patients received oral abexinostat 30, 45, or 60 mg/m(2) bid in a 3 + 3 design in three 21-day schedules: 14 days on trea...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-015-0206-x
更新日期:2015-04-01 00:00:00
abstract::Flavone acetic acid (FAA) was incubated for 1 to 48 hr with 3 established human colon cancer cell lines endowed with distinct degrees of phenotypic properties. All 3 lines responded to FAA in almost identical fashion; when incubated with the drug for only 1 hr, an initial decrease in survival was observed for concentr...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00173501
更新日期:1986-01-01 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
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/BF00216931
更新日期:1990-02-01 00:00:00
abstract::Bombesin/gastrin-releasing peptides (BN/GRP) were shown to bind selectively to cell surface receptors, stimulating the growth of various types of malignancies in murine and human models. The novel BN/GRP synthetic receptor antagonist, RC-3095, was able to produce long-lasting tumor regressions in murine and human tumo...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-006-6886-5
更新日期:2006-09-01 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
pub_type: 临床试验,杂志文章
doi:10.1023/a:1005989519350
更新日期:1997-01-01 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
pub_type: 临床试验,杂志文章
doi:10.1007/BF00198593
更新日期:1990-11-01 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
pub_type: 杂志文章
doi:10.1007/BF00180811
更新日期:1996-01-01 00:00:00
abstract::Over forty papers describing correlations between in vitro human tumor sensitivity to a variety of chemotherapeutic agents and the in vivo response of patients to those agents have been published since the publication in 1978 by Salmon and Hamburger of their results of a human tumor colony-forming chemosensitivity ass...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1007/BF00173788
更新日期:1984-01-01 00:00:00
abstract::Acquired resistance to tamoxifen (Tam) is a critical problem in breast cancer therapy. Therefore, new potential strategies for Tam-resistant breast cancer are needed recently. In this study, we synthesized a novel histone deacetylase (HDAC) inhibitor, MHY218, for the development of potent inhibitors of HDAC and evalua...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9752-z
更新日期:2012-10-01 00:00:00
abstract::Rolapitant is a neurokinin-1 receptor antagonist that is approved in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting (CINV) associated with initial and repeat courses of emetogenic cancer chemotherapy, including but not limited to highly emetogenic chemotherapy. Her...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/s10637-018-0638-1
更新日期:2019-02-01 00:00:00
abstract::Nafazatrom, a synthetic pyrazolinone derivative, has been shown to have substantial antitumor activity in vitro and antitumor and antimetastatic activity in experimental animal systems. The drug has produced no substantial toxicity in preclinical studies and during limited human trials. A phase I clinical trial with t...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00179592
更新日期:1986-01-01 00:00:00
abstract::Chemoprevention opens new perspectives in the prevention of cancer and other degenerative diseases. Use of target-organ biological models at the histological and genetic levels can markedly facilitate the identification of potential chemopreventive agents. Our aim was to study the chemopreventive efficacy of pronyl-ly...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9122-7
更新日期:2008-12-01 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
pub_type: 临床试验,杂志文章
doi:10.1007/BF00874443
更新日期:1994-01-01 00:00:00