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Gestational Trophoblastic Neoplasia
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Several other anti-cancer agents have been shown to have activity in GTN, including taxanes, gemcitabine, capecitabine. and pemetrexed either alone or in combination with platinum.56 We developed a regimen comprising paclitaxel and etoposide alternating every 2 weeks with paclitaxel and cisplatin (TE/TP; see Table 23.8), which has activity in patients with germ cell tumors and GTN that have failed prior treatment.158–160 This regimen is much less toxic than EP/EMA and in limited data, appears to have similar efficacy in salvaging EMA/CO failures.157,160 In China, where floxuridine is well tolerated, this is used in combination with ActD, etoposide, and vincristine (FAEV) to salvage EMA/CO failures with similarly good effect.161 The FAEV regimen is now also being used as initial therapy for high-risk patients in China.162
Microparticulate Carriers as a Therapeutic Option in Regional Cancer Therapy: Clinical Considerations
Published in Neville Willmott, John Daly, Microspheres and Regional Cancer Therapy, 2020
J. H. Anderson, Colin S. McArdle, T. G. Cooke
The pharmacokinetic principles underlying embolization have been confirmed in animal and human studies. Regional advantage is reflected in diminished systemic toxicity and encouraging tumor responses. There is little evidence of increased local toxicity in most studies, although target organs are subjected to intensified treatment compared with systemic therapy. Whether response rates are superior to those achievable with conventional systemic chemotherapy or external beam radiotherapy remains open to debate because there have been so few randomized controlled trials. Furthermore, it is not known if improved tumor response equates with prolonged survival. Lessons may be learned from experience with hepatic arterial chemotherapy for colorectal metastases in which the survival advantage is equivocal. Thus, in a prospective randomized trial (69 patients) to compare intra-arterial 5-fluoro-2′-deoxyuridine (floxuridine) with systemic 5-FU, despite a significantly higher response rate in the liver with regional chemotherapy (48% versus 21%), no survival advantage was seen.47 However, in a similar study (166 patients), hepatic arterial chemotherapy with 5-fluoro-2′-deoxyuridine conferred a statistically significant survival advantage.48
The Liver and the Biliary System
Published in E. George Elias, CRC Handbook of Surgical Oncology, 2020
Patients who have unresectable disease with no extrahepatic spread have been treated in the past with intrahepatic infusion of 5-fluorouracil (5-FU). However, a controlled prospective randomized study by the Central Oncology Group showed that such an approach had no advantage in improving the survival over systemic chemotherapy by 5-FU.5 The availability of an implantable infusion pump has caused a renewed interest in continuous infusion therapy with floxuridine (FUDR) especially in patients with metastatic colorectal carcinomas to the liver. Again, data are not available to prove whether prolongation of survival with such implantable drug infusion pumps warrants the widespread use of this expensive approach.6 We must also keep in mind, that the pump, whether it is implantable or externally placed, does not cure cancer. What affects the cancer is the drug that is delivered by such a pump. As of today, there is no proof that intrahepatic infusion of FUDR is superior to 5-FU given systemically. In addition, the continuous intrahepatic infusion of FUDR has resulted in some toxicity such as chemical hepatitis and sclerosing cholangitis.7
Pancreatic Cancer: A Review of Current Treatment and Novel Therapies
Published in Journal of Investigative Surgery, 2023
Hordur Mar Kolbeinsson, Sreenivasa Chandana, G. Paul Wright, Mathew Chung
Hepatic arterial infusion (HAI) therapy involves placing a catheter into the hepatic arterial vasculature (via gastroduodenal artery) supplying the liver and infusing chemotherapy directly into the liver. The benefits of HAI manifest in lower systemic toxicity and higher gradient of chemotherapy in the liver using certain agents [101]. The benefits of HAI therapy in the setting of liver metastases from colorectal cancer have long been recognized [102]. A few small studies have been conducted with HAI utilized as adjuvant treatment [103–105] as well as for metastatic PDAC [106]. They all have shown benefits to some extent. The non-randomized trial by Wang et al. compared 43 patients receiving adjuvant 2 cycles HAI chemotherapy followed by 4 cycles systemic chemotherapy (both consisting of 5-FU and gemcitabine) to 44 patients receiving adjuvant systemic gemcitabine + 5-FU alone [105]. Although 5-year disease-free probability was the same for both groups, the HAI group had significantly better 5-year overall survival probability (hazard ratio (HR) 0.60) and hepatic metastases-free survival (HR 0.50). Ohigashi et al and Beger et al described 53% 3-year survival and 54% 4-year survival, respectively, with the use of HAI chemotherapy in the adjuvant setting [103, 104]. Another small study by Tajima et al on patients with hepatic recurrence after resection showed a response rate in 6 out of 7 patients (85%) [106]. There is currently a phase 2 trial ongoing using floxuridine-based HAI chemotherapy for patients with liver metastases after PDAC resection (NCT03856658).
Initial systemic chemotherapeutic and targeted therapy strategies for the treatment of colorectal cancer patients with liver metastases
Published in Expert Opinion on Pharmacotherapy, 2019
Anas M Saad, Omar Abdel-Rahman
The use of HAI has also been studied in the settings of unresectable CRC-LM. However, a meta-analysis that included 10 randomized trials recommended against using fluoropyrimidine-based HAI monotherapy in this setting due to the failure of demonstrating clinically significant benefits [72]. On the other hand, a recent phase II trial assessed the use of Irinotecan-oxaliplatin-5-fluorouracil-based HAI with cetuximab in patients with unresectable KRAS wild-type CRC-LM and found a 30% conversion rate into resectable disease [73]. Another phase II trial also investigated the use of floxuridine-HAI in addition to the best chemotherapy regimen in patients with unresectable CRC-LM and found this treatment to be associated with a 47% conversion rate into a resectable disease [74]. Another recent phase II trial found a 52% conversion rate following the administration of Floxuridine-based HAI in combination with systemic oxaliplatin/irinotecan or 5-FU/leucovorin/irinotecan chemotherapy in patients with unresectable CRC-LM [75].
Translation of combination nanodrugs into nanomedicines: lessons learned and future outlook
Published in Journal of Drug Targeting, 2018
Qingxin Mu, Jesse Yu, Lisa A. McConnachie, John C. Kraft, Yu Gao, Gaurav K. Gulati, Rodney J. Y. Ho
Although the concept of combination therapy in nanomedicine research has existed for several years, only a few formulations are on the path for clinical translation, and some have recently been approved. CPX-1 and CPX-351 are examples of liposome-based DcNP formulations for cancer chemotherapy that are being translated into nanomedicine. CPX-1 contains drugs irinotecan and floxuridine and CPX-351 contains daunorubicin and cytarabine [48]. Both CPX-1 and CPX-351 employ a similar liposomal platform (enclosed lipid bilayer capable of encapsulating water soluble drugs and insoluble drug precipitates) to carry two drugs. These liposomes are composed of distearoylphosphatidycholine (DSPC) and distearolyphosphatidygylcerol (DSPG) as excipients to produce DcNPs exhibiting ∼100 ± 20 nm diameters (Table 2). In human studies, the accumulation ratio of the chemotherapeutics irinotecan and floxuridine was found to be proportional to the initial formulation ratio (1:1 molar) [49].