Efficacy and safety of capecitabine in combination with docetaxel and mitomycin C in patients with pre-treated pancreatic, gallbladder, and bile duct carcinoma

Kruth, Jens; Nissen, Johanna; Ernst, Thomas; Kripp, Melanie; Lukan, Nadine; Merx, Kirsten; Hofmann, Wolf‐Karsten; Hochhaus, Andreas; Hofheinz, Ralf–Dieter

doi:10.1007/s00432-010-0843-6

Cited by 4 publications

(5 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The current standard regimen for untreated advanced biliary cancer is the combination of cytotoxic chemotherapy with gemcitabine and cisplatin, but the disease is nearly always fatal, with a median survival that remains less than one year 4 . In addition, trials for second-line therapy in refractory biliary cancer have been disappointing, highlighting the urgent need to develop new and effective therapies 5 6 7 .…”

mentioning

confidence: 99%

Results of an abbreviated phase-II study with the Akt Inhibitor MK-2206 in Patients with Advanced Biliary Cancer

Ahn

Wei

et al. 2015

Sci Rep

View full text Add to dashboard Cite

Biliary cancers (BC) are rare, chemoresistant and are associated with a poor prognosis. Targeting the Akt pathway is of significance in BC. We hypothesized that the allosteric inhibitor MK-2206 will be active in BC. This was a multi-institutional phase II study of MK-2206 given to patients with advanced, refractory BC. The primary end point was overall response rate. We also characterized pharmacokinetic profiles of MK-2206 in these patients and explored its potential correlation with clinical outcomes. Eight patients were enrolled prior to early termination of the trial. All patients had received prior systemic therapy. The best response observed was stable disease, exceeding 12 weeks in two patients. Toxicities were mild and tolerable. MK-2206 exhibited a pharmacokinetic profile with an apparent slow absorption followed by biphasic elimination in these patients with BC. No significant association was observed between the pharmacokinetic properties of MK-2206 and clinical outcomes. MK-2206 as a single-agent in BC is tolerable with pharmacokinetic properties similar to patients with other solid tumors. No clinical activity was observed in this limited population. Further development of Akt inhibitors may need to focus on combinations with other molecular targeted agents, conventional cytotoxic chemotherapy and prospective patient selection.

show abstract

mentioning

confidence: 99%

Results of an abbreviated phase-II study with the Akt Inhibitor MK-2206 in Patients with Advanced Biliary Cancer

Ahn

Wei

et al. 2015

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Gemcitabine related combinations, like GOFL, GEMOXEL or GEMTG, exhibited similar median overall survival with a range of 6.3 to 8.7 and merited further investigations. Doxorubicin, mitomycin and 5-fluorouracil/ capecitabine were used together as salvage therapy for billio-pancreatic cancer in two trials Kruth et al, 2010) and got an average median overall survival of 6.75 months, not bad results in terms of second-line therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Treatment that consisted of capecitabine, doxorubicin, and mitomycin-C was applied to 28 pretreated patients suffering from pancreatic, gallbladder and bile duct cancer in a trial conducted by Kruth et al (2010) and resulted in a high tumor control rate (6 patients achieving partial remissions, 7 achieving minor remissions, 6 having stable disease), 4.5 months median progressionfree survival, 6.8 months median overall survival and a safety profile.…”

Section: Doxorubicin Mitomycin and 5fluorouracil/capecitabinementioning

confidence: 99%

A review of clinical trials of chemotherapy for pancreatic cancer

Zhu¹

2012

J. Cancer Res. Exp. Oncol.

View full text Add to dashboard Cite

Chemotherapy is playing an important role in treating pancreatic cancer, either when used alone or when combined with surgery and radiotherapy. We summarized 80 eligible clinical trials published from January in 2006 to June in 2011 and discussed the future development of chemotherapy in the treatment of pancreatic cancer. All the clinical trials were divided into 5 groups: single-agent regimen (14 trials), binary combination (27 trials), triple or more combination (13 trials), neoadjuvant/preoperative chemotherapy (4 trials), and targeted therapy (22 trials). Gemcitabine used alone was confirmed effective in 5 trials, while fixed-dose-rate gemcitabine showed apparent toxicities. In 4 trials, oral S-1 seemed feasible and convenient as a second-line agent. Explorations of irinotecan and paclitaxel loaded polymeric micelle as single agents also got positive outcomes. Many trials focused on the gemcitabine-based combinations with drugs like cisplatin, S-1, oxaliplatin, glufosfamide, etc., and some got positive results. Due to the occurrences of gemcitabine-resistance or even 5-fluorouracil-resistance, second-line combinations have become important and some have shown considerable value. Apart from the binary combination, three or more drugs used together, like FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) and FOLFIRI (5-fluorouracil, leucovorin, and irinotecan) also exhibited promising activity. A new method called neoadjuvant therapy (treating patients with drugs before surgery) was investigated in 4 trials with encouraging outcomes. In addition, some sites related to tumor cell proliferation and metastasis, such as growth factor receptor, CTLA-4 (CD152), the mammalian target of rapamycin, cyclooxygenase-2, cholecystokinin-2 receptor, leukotriene B4 receptor, peroxisome proliferator-activated receptor gamma and proto-oncogene, have been explored in some clinical trials and are worth further researches.

show abstract

“…The current standard regimen for untreated advanced BTC is a combination of cytotoxic chemotherapy with gemcitabine and cisplatin, and the disease remains universally fatal, with a median survival that remains less than one year [ 3 ]. The poor outcomes with first-line treatment and absence of approved therapies in the refractory setting highlight the need to develop new and more effective treatments for biliary cancers [ 4 - 6 ].…”

Section: Introductionmentioning

confidence: 99%

Whole-exome tumor sequencing study in biliary cancer patients with a response to MEK inhibitors

et al. 2015

View full text Add to dashboard Cite

We previously conducted a phase-II study with selumetinib (AZD6244), a small molecule inhibitor of MEK1/2, in advanced biliary tract cancers (BTC), where the primary endpoint was response rate. Several patients experienced objective response. These findings were confirmed with MEK162 in a similar patient population. To assess for tumor-specific genetic variants that mediate sensitivity to MEK inhibition in BTC, we performed whole-exome sequencing in patients with an objective response to selumetinib. Normal and tumor DNA from FFPE tissue from two patients who experienced an objective response underwent whole-exome sequencing. Raw sequence reads were processed with GATK workflow and tumor specific variants were identified using MuTect and VarScan2. Ensemble Variant Effect Predictor was used to determine functional consequences of these variants. Copy number changes and potential gene fusion events were also screened. Findings were compared to assess for any commonality between the two tumor samples, and whether the identified variants were intrinsic to the MAPK pathway. 1169 and 628 tumor-specific variants were identified in the two samples. Further analysis demonstrated 60 and 53 functional and novel variants, respectively. Of the identified tumor-specific variants, fusion events or copy number changes, no commonality was seen. Several variants in genes associated with ERK signaling were present in each tumor sample. Although there were no common tumor-specific variants in the two patients who exhibited an objective response to selumetinib, several genes associated with ERK signaling were identified. Confirmatory studies investigating the role of the identified genes and other potential tumor independent factors need further investigation.

show abstract

Efficacy and safety of capecitabine in combination with docetaxel and mitomycin C in patients with pre-treated pancreatic, gallbladder, and bile duct carcinoma

Abstract: In all, the DocMitoCape regimen exhibited a favorable safety profile and a high rate of tumor stabilizations in patients with pre-treated gallbladder, bile duct and pancreatic carcinoma. It might be considered after failure of standard regimens in these types of cancer.

Cited by 4 publications

References 28 publications

Results of an abbreviated phase-II study with the Akt Inhibitor MK-2206 in Patients with Advanced Biliary Cancer

Results of an abbreviated phase-II study with the Akt Inhibitor MK-2206 in Patients with Advanced Biliary Cancer

A review of clinical trials of chemotherapy for pancreatic cancer

Whole-exome tumor sequencing study in biliary cancer patients with a response to MEK inhibitors

Contact Info

Product

Resources

About