Abstract:
BACKGROUND:Quinacrine plus a fluoropyrimidine has in vivo efficacy against metastatic colorectal cancer (mCRC). This phase 1b trial evaluated the combination of quinacrine plus capecitabine in patients with treatment-refractory mCRC. PATIENTS AND METHODS:Using a modified Simon accelerated titration design, adults with treatment-refractory mCRC were treated with capecitabine 1000 mg/m2 twice daily for 14/21-day cycle, and escalating doses of quinacrine 100 mg daily, 100 mg twice daily, and 200 mg twice daily for 21 days. The primary endpoint was identifying the maximum tolerated dose, determining tolerability and safety. In an expansion cohort, it was overall response rate and time to tumor progression (TTP). RESULTS:Ten patients (median age of 60 years) were treated in phase 1b. The first 2 quinacrine dosing levels were well tolerated. Dose-limiting toxicities were seen in 3 patients treated with quinacrine 200 mg twice daily. Five additional patients tolerated quinacrine 100 mg twice daily without further dose-limiting toxicities, thus establishing the maximum tolerated dose. Seven additional expansion-cohort patients enrolled onto the study before quinacrine manufacturing ceased within the United States. Five patients experienced stable disease, 1 partial response, and 10 disease progression. Median TTP overall was 2.12 months and median overall survival 5.22 months for the 17 patients. CONCLUSION:Capecitabine and quinacrine can be safely administered at the maximum tolerated dose of capecitabine 1000 mg/m2 by mouth twice daily on days 1-14 and quinacrine 100 mg by mouth twice daily on days 1-21 of a 21-day cycle in mCRC patients. Although the expansion study was halted early, TTP was in line with other studies of refractory mCRC, suggesting activity of this regimen in heavily pretreated patients.
journal_name
Clin Colorectal Cancerjournal_title
Clinical colorectal cancerauthors
Winer A,Denlinger CS,Vijayvergia N,Cohen SJ,Astaturov I,Dotan E,Gallant JN,Wang EW,Kunkel M,Lim B,Harvey HA,Sivik J,Korzekwa K,Ruth K,White K,Cooper HS,Ross EA,Zhou L,El-Deiry WSdoi
10.1016/j.clcc.2020.08.003subject
Has Abstractpub_date
2020-08-19 00:00:00eissn
1533-0028issn
1938-0674pii
S1533-0028(20)30107-9pub_type
杂志文章abstract:BACKGROUND:With improved survival and longer duration of treatment, clinicians managing metastatic colorectal cancer (mCRC) increasingly consider intermittent (IC) or maintenance chemotherapy (MC), but the effect of these treatment modifications on real-world outcomes is unclear. PATIENTS AND METHODS:Using a populatio...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2017.10.011
更新日期:2018-03-01 00:00:00
abstract:BACKGROUND:Individually, oxaliplatin and irinotecan have substantial activity in metastatic colorectal cancer (CRC) in combination with 5-fluorouracil/leucovorin. A combination regimen using all 4 agents could potentially increase response rates in CRC. PATIENTS AND METHODS:A multicenter phase II trial of oxaliplatin ...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,多中心研究
doi:10.3816/CCC.2007.n.017
更新日期:2007-05-01 00:00:00
abstract::Adult intussusception is a rare occurrence and, unlike in childhood, is usually associated with an underlying tumor. Although computed tomography (CT) imaging can identify an intussusception and point toward a cause, diagnosis is challenging if it is only intermittent. When an intussusception presents in the context o...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2008.n.028
更新日期:2008-05-01 00:00:00
abstract:BACKGROUND:The safety of bevacizumab in older mCRC patients is poorly understood. The purpose of this analysis was to determine the prevalence, incidence, and risk factors for treatment-related AEs in older bevacizumab recipients. PATIENTS AND METHODS:Patients age ≥65 were identified from SEER-Medicare and categorized...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2012.11.004
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND:Systemic chemotherapy increases the possibility of resection in patients with initially unresectable colorectal cancer (CRC), especially patients with hepatic metastasis. However, the predictive factors and prognosis of conversion to resection after chemotherapy in patients with various organ metastases rema...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2017.10.002
更新日期:2018-03-01 00:00:00
abstract::Colorectal cancer (CRC), one of the most common malignancies worldwide, is often diagnosed at an advanced stage, and resistance to chemotherapeutic and existing targeted therapy is a major obstacle to its successful treatment. New targets that offer alternative clinical options are therefore urgently needed. Recently,...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.1016/j.clcc.2016.06.006
更新日期:2017-03-01 00:00:00
abstract:BACKGROUND:The prognostic value of tumor sidedness in metastatic colorectal cancer (CRC) has been established, but its impact on nonmetastatic disease remains unclear. Our study aimed to explore the prognostic effect of tumor sidedness by subgroup survival analyses, according to histology and tumor grade in stage I-IV ...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2018.10.005
更新日期:2019-03-01 00:00:00
abstract:BACKGROUND:New treatment modalities and a growing understanding of the complex genetic tumor landscape have improved the outcome of colorectal cancer (CRC) patients. Nonetheless, more individualized treatment regimens, taking individual tumor characteristics into account, have been recently postulated and prognostic bi...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2018.02.008
更新日期:2018-06-01 00:00:00
abstract:BACKGROUND:ERBB2 amplification occurs in 5% of RAS wild-type metastatic colorectal cancer (mCRC) and it has been shown to be a target for treatment with 2 HER2-directed combinations of trastuzumab and lapatinib or trastuzumab and pertuzumab. We present long-term clinical results of trastuzumab and lapatinib (HERACLES-A...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2020.06.009
更新日期:2020-12-01 00:00:00
abstract:UNLABELLED:Two identical randomized controlled trials designed to optimize adjuvant treatment of colon cancer (CC) (n =855) and rectal cancer (RC) (n = 796) were performed. Long-term evaluation confirmed that the addition of folinic acid (FA) to 5-fluorouracil (5-FU) improved 7-year overall survival (OS) in CC but not ...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clcc.2012.07.005
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND:Köhne prognostic score is used to classify patients with metastatic colorectal cancer (mCRC) as high, intermediate, or low risk. Using data from 2 phase III trials, we analyzed survival in patients categorized according to Köhne prognostic category and virus-induced rapidly accelerated fibrosarcoma murine sa...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2017.09.006
更新日期:2018-03-01 00:00:00
abstract:INTRODUCTION:In studies of colorectal cancer, the elderly have been frequently underrepresented because comorbid conditions and functional status often lead to study exclusion. For elderly patients with an indication for neoadjuvant chemoradiotherapy (nCRT), physicians usually decide using clinical factors whether nCRT...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2018.03.004
更新日期:2018-09-01 00:00:00
abstract:BACKGROUND:Initial treatment with either neoadjuvant chemoradiation (CRT) or induction FOLFOX (5-Fluorouracil, leucovorin, and oxaliplatin) chemotherapy followed by CRT is considered standard treatment for locally advanced rectal cancer. We compared patient-reported outcomes (PRO) during CRT in patients who had receive...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2019.04.001
更新日期:2019-09-01 00:00:00
abstract::The development of brain metastases originating from colorectal cancer (CRC) is an infrequent phenomenon occurring in < 5% of patients. Yet, it is feasible that physicians will be diagnosing more patients with brain metastases because of the prolonged survival in our current patient population. The anti-angiogenic age...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2008.n.010
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:The Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation (ICECREAM) study assessed the efficacy of cetuximab monotherapy compared with cetuximab combined with chemotherapy for quadruple wild-type (KRAS, NRAS, BRAF, or P13KCA exon 20) metastatic colorectal cancer. PATIENTS AND METHODS:Patients w...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clcc.2018.06.002
更新日期:2018-12-01 00:00:00
abstract::The multiplicity of chemotherapy regimens currently available to treat colorectal cancer in the first-line setting precludes the identification of a single standard regimen for front-line therapy. The previous standard, 5-fluorouracil (5-FU), formerly the only agent with any significant activity against colorectal can...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/ccc.2004.s.002
更新日期:2004-06-01 00:00:00
abstract:PURPOSE:The tumor-activated fluoropyrimidine capecitabine achieves response rates superior to those of bolus 5-fluorouracil/leucovorin (5-FU/LV) as first-line treatment for metastatic colorectal cancer (CRC), with favorable safety and fewer hospitalizations. Capecitabine is also at least as effective as bolus 5-FU/LV i...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/ccc.2005.n.021
更新日期:2005-07-01 00:00:00
abstract::The discovery of the key role of the epidermal growth factor receptor (EGFR) and its downstream signaling effectors in the pathophysiology of colorectal cancer (CRC) has ushered in the clinical use of targeted therapies in the treatment of metastatic CRC (mCRC). The anti-EGFR monoclonal antibodies cetuximab and panitu...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.1016/j.clcc.2015.05.006
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:Colorectal cancer (CRC) is a common malignancy. There is growing evidence that CRC incidence is increasing in the younger population. There is controversy surrounding the prognosis of young patients with CRC. In this study we reviewed Australian patients with metastatic CRC (mCRC) who were younger than 40 ye...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2015.07.005
更新日期:2016-03-01 00:00:00
abstract:OBJECTIVE:The purposes of this study were to confirm the definite metastasis and micrometastasis rate of upward and lateral lymph nodes of mid-to-low rectal cancer at stage II and stage III, and to evaluate the feasibility and safety of laparoscopic radical correction combined with extensive lymphadenectomy and pelvic ...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2011.03.025
更新日期:2011-09-01 00:00:00
abstract::Regimens based on flouropyrimidines (eg, 5-fluorouracil [5-FU] and capecitabine) are the mainstay of chemotherapy for several malignancies, including colon, pancreatic, upper gastrointestinal, and breast cancers. Warfarin is one of the most commonly used oral anticoagulants. Patients receiving concomitant capecitabine...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/ccc.2005.n.028
更新日期:2005-09-01 00:00:00
abstract:BACKGROUND:As of 2006, bevacizumab was available for the treatment of metastatic colorectal cancer (mCRC) in British Columbia (BC). This study compares survival between referred patients diagnosed with mCRC in 2003/2004 (pre-bevacizumab era) and 2006 (bevacizumab era). PATIENTS AND METHODS:The BC cancer agency (BCCA) ...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2011.03.004
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND:Screening protocols for colorectal cancer are broadly recommended and effective in reducing mortality. However, populations from different age groups can harbor distinct pathologic and molecular profiles that can also be influenced by screening and polyp resection, especially in older ages. PATIENTS AND MET...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2020.06.004
更新日期:2020-12-01 00:00:00
abstract::Several anticancer therapies have been developed to block angiogenesis, a key mechanism in tumor growth and metastasis. The predominantly cytostatic action of these compounds makes an assessment of their clinical activities inadequate if based only on the reduction of the tumor dimensions, as this may not reflect thei...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.1016/j.clcc.2014.12.002
更新日期:2015-03-01 00:00:00
abstract::The use of adjuvant chemotherapy has improved survival in early-stage colon cancer. Ongoing adjuvant clinical trials are evaluating the addition of targeted therapies to standard chemotherapy regimen. Preliminary results with bevacizumab were disappointing. Also, cetuximab added to chemotherapy does not seem to be bet...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2010.n.039
更新日期:2010-12-01 00:00:00
abstract:BACKGROUND:Few patients with metastatic colorectal cancer (mCRC) are candidates for resection of their hepatic disease. Yttrium-90 ((90)Y) radioembolization has promise in the treatment of unresectable mCRC. We conducted a retrospective study to assess the efficacy in patients with refractory mCRC who underwent (90)Y r...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2011.12.002
更新日期:2012-09-01 00:00:00
abstract:INTRODUCTION:Hepatic arterial infusion chemotherapy (HAIC) is a treatment used for liver metastases (LM) of colorectal cancer (CRC). Because of its technical conditions, it has been used in only a few experienced centers in France. Our aim was to evaluate its feasibility, efficacy and tolerance in 4 centers. METHODS:C...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,多中心研究
doi:10.1016/j.clcc.2017.03.003
更新日期:2017-12-01 00:00:00
abstract::As new improvements in the treatment of colorectal cancer have become available, it has become important to understand the benefits of new therapies or the deleterious effects stemming from the increased risk of toxicity. In particular, a more rational approach to adjuvant chemotherapy for patients with stage II/III d...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/ccc.2006.n.019
更新日期:2006-05-01 00:00:00
abstract::Combination protocols of 5-fluorouracil/leucovorin (5-FU/LV) plus irinotecan or oxaliplatin have demonstrated high activity in metastatic colorectal cancer. Capecitabine, an oral 5-FU prodrug, may replace infusional 5-FU/LV in combination protocols with irinotecan or oxaliplatin. We therefore initiated a phase II stud...
journal_title:Clinical colorectal cancer
pub_type: 临床试验,杂志文章
doi:10.3816/ccc.2004.n.009
更新日期:2004-05-01 00:00:00
abstract::In the past 10 years, overall survival and disease-free survival of patients with colorectal cancer (CRC) has improved substantially because of a combination of factors: (1) more accurate staging as a result of advances in imaging technology; (2) refinements in surgical technique; (3) 'curative' metastasectomy for pat...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2009.n.013
更新日期:2009-03-01 00:00:00