Intratumoral chemotherapy with a sustained-release drug delivery system inhibits growth of human pancreatic cancer xenografts

Smith, Jill P.; Stock, Elizabeth; Orenberg, Elaine K.; Yu, Ning; Kanekal, Sarathchandra; Brown, Dennis

doi:10.1097/00001813-199512000-00002

Cited by 22 publications

(5 citation statements)

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“…[ 19 ] Local delivery of chemotherapeutic drugs is recognized as a potential method of delivering a drug to the target site with minimal systemic exposure. Smith et al [ 20 ] reported that intratumoral chemotherapy with a sustained-release drug delivery system could inhibit growth of human pancreatic cancer xenografts. The present study, however, found that LAPC patients who were treated with intraoperative interstitial sustained-release 5-fluorouracil chemotherapy had worse OS compare to those without intraoperative interstitial sustained-release 5-fluorouracil chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Long-term results of intraoperative electron beam radiation therapy for nonmetastatic locally advanced pancreatic cancer

Chen

Che²,

Zhang³

et al. 2016

Medicine

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Section: Discussionmentioning

confidence: 99%

Long-term results of intraoperative electron beam radiation therapy for nonmetastatic locally advanced pancreatic cancer

Chen

Che²,

Zhang³

et al. 2016

Medicine

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“…25 In another study examining the efficacy of a novel drug delivery system, BXPC3 xenografts showed a 72-79% inhibitory response when treated with 5-fluorouracil, cisplatin, or doxorubicin. 26 Recent studies using trocar-implanted PDAC tumors (HPAC and KCL-MOH1) in severe combined immunodeficient (SCID) mice, evaluated the efficacy of gemcitabine, 5-fluorouracil, taxol, Ara-C, and novel biological agents Bryostatin 1 and Auristatin-PE on PDAC tumor growth. These studies revealed that treatment with gemcitabine was the most effective agent (T/C = 3) followed by Ara-C (T/C = 17), and Bryostatin (T/C = 38); taxol and 5-fluorouracil were ineffective against the tumors, and Auristatin-PE was toxic at the dose used in the study.…”

Section: Discussionmentioning

confidence: 99%

The Novel Trk Receptor Tyrosine Kinase Inhibitor CEP‐701 (KT‐5555) Exhibits Antitumor Efficacy against Human Pancreatic Carcinoma (Panc1) Xenograft Growth and In Vivo Invasiveness

Miknyoczki

Dionne²,

Klein‐Szanto

et al. 1999

Annals of the New York Academy of Sciences

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The survival rate for patients with pancreatic ductal adenocarcinoma (PDAC) is among the poorest for all cancers. The factors that contribute to this poor prognosis are lack of effective early detection, high rate of metastases and a generally refractory response to available treatment modalities. The most commonly used treatment methods--chemotherapy and radiation therapy--are mainly used for symptom palliation, with surgery being the only "curative" treatment option. The use of combinations of treatment modalities is the only therapy available to patients with locally advanced disease or that which is surgically unresectable. These options are still not sufficient to increase patient survival time significantly. The aggressive behavior and poor prognosis of this cancer is associated with an increased expression of many growth factors and their cognate receptors. We have demonstrated previously the aberrant expression of the Trk receptors (Trks A, B, and C) in PDAC specimens and human PDAC-derived cell lines and a biphasic, dose-dependent response of specific neurotrophic agents on the in vitro invasiveness of PDAC cells. Based on these data we have evaluated the therapeutic potential of inhibiting neurotrophin-Trk interactions using a selective Trk tyrosine kinase inhibitor (CEP-701) on subcutaneous (s.c.) and tracheal xenografts derived from the poorly differentiated PDAC cell line, Panc1. We demonstrate that CEP-701 administration at 10 mg/kg s.c. BID for 21 days inhibited tumor growth of the Panc1 s.c. xenografts in a statistically-significant manner (p < 0.01) compared to vehicle controls, in the absence of morbidity and mortality. A T/C value of 25% was observed for CEP-701-treated s.c. xenografts. In addition, CEP-701 administration inhibited tumor cell invasion in the s.c. tracheal xenograft model of in vivo invasiveness. Taken together, these data suggest that further studies are warranted to evaluate CEP-701 as a potential therapeutic agent in the treatment of PDAC.

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“…However, these investigators felt that this approach still failed to consistently cure these animal tumours. Using nude mice xenografts of a human pancreatic adenocarcinoma (BxPC-3), Smith et al (1994) examined intratumoral delivery of uorouracil (50 mg kg 1 ), cisplatin (8 mg kg 1 ), or doxorubicin (8 mg kg 1 ) in a collagen gel containing epinephrine (intended to prolong drug delivery by local vasoconstriction). Doxorubicin was most potent but all intratumoral systems reduced tumour burden by " 70% .…”

Section: Animal Intratumoral Chemotherapy Studiesmentioning

confidence: 99%

Intratumoral cancer chemotherapy and immunotherapy: opportunities for nonsystemic preoperative drug delivery

Goldberg

Hadba

Almond

et al. 2002

Journal of Pharmacy and Pharmacology

175

143

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The recent literature documents the growing interest in local intratumoral chemotherapy as well as systemic preoperative chemotherapy with evidence for improved outcomes using these therapeutic modalities. Nevertheless, with few exceptions, the conventional wisdom and standard of care for clinical and surgical oncology remains surgery followed by radiation and/or systemic chemotherapy, as deemed appropriate based on clinical ndings. This, in spite of the fact that the toxicity of conventional systemic chemotherapy and immunotherapy affords limited effectiveness and frequently compromises the quality of life for patients. Indeed, with systemic chemotherapy, the oncologist (and the patient) often walks a ne line between attempting tumour remission with prolonged survival and damaging the patient's vital functions to the point of death. In this context, it has probably been obvious for more than 100 years, due in part to the pioneering work of Ehrlich (1878), that targeted or localized drug delivery should be a major goal of chemotherapy. However, there is still only limited clinical use of nonsystemic intratumoral chemotherapy for even those high mortality cancers which are characterized by well de ned primary lesions i.e. breast, colorectal, lung, prostate, and skin.There has been a proliferation of intratumoral chemotherapy and immunotherapy research during the past two to three years. It is therefore the objective of this review to focus much more attention upon intratumoral therapeutic concepts which could limit adverse systemic events and which might combine clinically feasible methods for localized preoperative chemotherapy and/or immunotherapy with surgery. Since our review of intratumoral chemo- Given the state-of-the-art in clinical and surgical oncology, and the advances that have been made in intratumoral drug delivery, minimally invasive tumour access i.e. ne needle biopsy, new drugs and drug delivery systems, and preoperative chemotherapy, it is timely to present a review of studies which may suggest future opportunities for safer, more effective, and clinically practical non-systemic therapy. General perspective for traditional systemic therapiesThe toxicity of conventional systemic cancer chemotherapy and immunotherapy has severely limited the safety and eOE ectiveness of such therapy. The quality of life

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Intratumoral chemotherapy with a sustained-release drug delivery system inhibits growth of human pancreatic cancer xenografts

Cited by 22 publications

References 0 publications

Long-term results of intraoperative electron beam radiation therapy for nonmetastatic locally advanced pancreatic cancer

Long-term results of intraoperative electron beam radiation therapy for nonmetastatic locally advanced pancreatic cancer

The Novel Trk Receptor Tyrosine Kinase Inhibitor CEP‐701 (KT‐5555) Exhibits Antitumor Efficacy against Human Pancreatic Carcinoma (Panc1) Xenograft Growth and In Vivo Invasiveness

Intratumoral cancer chemotherapy and immunotherapy: opportunities for nonsystemic preoperative drug delivery

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