Granted Patent
B2
US 12,496,345 · App. 18/336,379 · Granted Dec 16, 2025
Method of treating cancer
Assignee:
Intensity Therapeutics, Inc.
A61K47/14A61K8/042A61K8/19A61K8/20A61K8/342A61K8/345A61K8/36A61K8/368A61K8/375A61K8/416A61K8/42A61K9/006A61K9/08A61K31/192A61K31/20A61K31/216A61K31/282A61K31/475A61K31/555A61K31/7032A61K31/7105A61K33/242A61K33/243A61K45/06A61K47/12A61K47/18A61Q5/12A61K9/0019A61K2800/30A61K2800/34A61K2800/524
View Patent ↗
Loading inventors, assignments & file history…
Abstract
The invention provides a method for treating cancer using a coadministration strategy that combines local codelivery of a therapeutic agent and an intracellular penetration enhancing agent, and optionally in further combination with local administration of an immunotherapeutic agent, such as a cancer vaccine or NKT agonist. The invention also provides a method for treating cancer using an intracellular penetration enhancing agent. The methods of the invention aim to substantially kill and/or destroy the target tumor cells, as well as those cancerous cells that have metastasized to other parts of the body.
Claims (8)
1 . A method of treating a breast cancer in a subject comprising administering intratumorally a therapeutically effective amount of a composition, wherein the composition comprises vinblastine or salt thereof, cisplatin and N-[8-(2-hydroxybenzoyl)amino]octanoic acid.
2 . The method of claim 1 , wherein the composition comprises 0.5 mg/mL cisplatin and 10 mg/mL N-[8-(2-hydroxybenzoyl)amino]octanoic acid.
3 . The method of claim 1 , wherein the breast cancer is a metastatic breast cancer.
4 . A method of treating a sarcoma in a subject comprising administering intratumorally a therapeutically effective amount of a composition, wherein the composition comprises vinblastine or salt thereof, cisplatin and N-[8-(2-hydroxybenzoyl)amino]octanoic acid.
5 . The method of claim 4 , wherein the composition comprises 0.5 mg/mL cisplatin and 10 mg/mL N-[8-(2-hydroxybenzoyl)amino]octanoic acid.
6 . The method of claim 4 , wherein the sarcoma is a soft tissue sarcoma.
7 . An intratumoral formulation comprising vinblastine or salt thereof, cisplatin and N-[8-(2-hydroxybenzoyl)amino]octanoic acid in a sterile liquid preparation, wherein the sterile liquid preparation is isotonic with the blood of the formulation's intended recipient.
8 . The intratumoral formulation of claim 7 , wherein the intratumoral formulation comprises 0.5 mg/mL of cisplatin and 10 mg/mL of N-[8-(2-hydroxybenzoyl)amino]octanoic acid.
Assignments (2)
CORRECTIVE ASSIGNMENT TO CORRECT THE ADDRESS OF THE ASSIGNEE PREVIOUSLY RECORDED ON REEL 67862 FRAME 494. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNOR HEREBY CONFIRMS THE ASSIGNMENT..
Recorded Aug 7, 2024
From: BENDER, LEWIS H.
To: INTENSITY THERAPEUTICS, INC.
Reel/Frame 068335/0243 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 27, 2024
From: BENDER, LEWIS H.
To: INTENSITY THERAPEUTICS, INC.
Reel/Frame 067862/0494 →
Continuity (9)
Continuation
PCTUS2013059841
· Sep 15, 2013
Provisional Application
61779509
· Mar 13, 2013
Provisional Application
61707733
· Sep 28, 2012
Provisional Application
61703890
· Sep 21, 2012
References Cited (157)
US 4978332A
· Luck et al.
· 1990
[cited by applicant]
US 5162115A
· Pietronigro
· 1992
[cited by applicant]
US 5679638A
· Teicher
· 1997
[cited by examiner]
US RE35748E
· Luck et al.
· 1998
[cited by applicant]
US 5866536A
· Leone-Bay et al.
· 1999
[cited by applicant]
US 5874402A
· Singh et al.
· 1999
[cited by applicant]
US 6110492A
· Alving et al.
· 2000
[cited by applicant]
US 7648695B2
· Dees et al.
· 2010
[cited by applicant]
US 9351997B2
· Bender
· 2016
[cited by applicant]
US 9636406B2
· Bender
· 2017
[cited by applicant]
US 20070049557A1
· Ahmed et al.
· 2007
[cited by applicant]
US 20070071677A1
· Park et al.
· 2007
[cited by applicant]
US 20090186802A1
· Alluis et al.
· 2009
[cited by applicant]
US 20090275654A1
· Brown
· 2009
[cited by applicant]
US 20110077297A1
· Jansen
· 2011
[cited by applicant]
US 20130156859A1
· Koshi et al.
· 2013
[cited by applicant]
US 20210077627A1
· Bender
· 2021
[cited by applicant]
AU 2017202970B2
· 2018
[cited by applicant]
CN 101928234A
· 2010
[cited by applicant]
EP 2897620A1
· 2015
[cited by applicant]
JP 2000507215A
· 2000
[cited by applicant]
JP 2001517694A
· 2001
[cited by applicant]
JP 2007538014A
· 2007
[cited by applicant]
WO WO9730705A1
· 1997
[cited by applicant]
WO WO9853799A2
· 1998
[cited by applicant]
WO WO9916427A1
· 1999
[cited by applicant]
WO WO0134130A1
· 2001
[cited by applicant]
WO WO03007869A2
· 2003
[cited by applicant]
WO WO2004081196A2
· 2004
[cited by applicant]
WO WO2005107462A2
· 2005
[cited by applicant]
WO WO2005117854A2
· 2005
[cited by applicant]
WO WO2006072070A2
· 2006
[cited by applicant]
WO WO2008095144A2
· 2008
[cited by applicant]
WO WO2011084061A1
· 2011
[cited by applicant]
WO WO2011112889A2
· 2011
[cited by applicant]
WO WO2012026508A1
· 2012
[cited by applicant]
WO WO2014018932A2
· 2014
[cited by applicant]
WO WO2014046983A1
· 2014
[cited by applicant]
F. Celikoglu et al., “Techniques for intratumoral chemotherapy of lung cancer by bronchoscopic drug delivery,” Cancer Therapy vol. 6, 2008, p. 545-552.
[cited by examiner]
Ajima, K. et al., “Enhancement of in vivo anticancer effects of cisplatin by incorporation inside single-wall carbon nanohorns,” ACS Nano., Oct. 2008, 2(10):2057-2064.
[cited by applicant]
Alani, A. W. G. et al., “Mechanistic Understanding of Oral Drug Absorption Enhancement of Cromolyn Sodium by an Amino Acid Derivative,” Pharmaceutical Research, 2008, 25(1):48-54.
[cited by applicant]
American Cancer Society, “Filgrastim,” WayBack Macine [Online], http://www.cancer.org/Treatment/TreatmentsandSideEffects/GuidetoCancerDrugs/filgrastim, Mar. 28, 2011, 3 pages.
[cited by applicant]
Amiji, M. M. et al., “Intratumoral administration of paclitaxel in an in situ gelling poloxamer 407 formulation,” Pharmaceutical Development and Technology, May 2002, 7(2):195-202.
[cited by applicant]
Bajaj, G. et al., “Drug delivery systems for intraperitoneal therapy,” Pharm Res., May 2010, 27(5):735-738. Epub Mar. 3, 2010.
[cited by applicant]
Barth, R. F. et al., “Neutron capture therapy of epidermal growth factor (+) gliomas using boronated cetuximab (IMC-C225) as a delivery agent,” Applied Radiation and Isotopes, 2004, 61:899-903.
[cited by applicant]
Benoit, L. et al., “Intraperitoneal cisplatin plus epinephrine and surgical debulking for the treatment of advanced peritoneal carcinomatosis in the rat,” Gastroenterol Clin Biol., Jan. 2000, 24(1):26-30.
[cited by applicant]
Bloom, N. D. et al., “Enhancement of tumor blood flow and tumoricidal effect of doxorubicin by intraportal epinephrine in experimental liver metastasis,” Arch Surg. Nov. 1987, 122(11):1269-1272.
[cited by applicant]
Braumann, C. et al., “Local and systemic chemotherapy with taurolidine and taurolidine/heparin in colon cancer-bearing rats undergoing laparotomy,” Clin Exp Metastasis, 2003, 20(5):387-394.
[cited by applicant]
Castro, D. J. et al., “Intratumoral cisplatin/epinephrine gel in advanced head and neck cancer: a multicenter, randomized, double-blind, phase III study in North America,” Head & Neck, Sep. 2003, 25(9):717-731.
[cited by applicant]
Celikoglu, F. et al., “Techniques for intratumoral chemotherapy of lung cancer by bronchoscopic drug delivery,” Cancer Therapy, 2008, 6:545-552.
[cited by applicant]
Cemazar, M. et al., “Intratumoral cisplatin administration in electrochemotherapy: antitumor effectiveness, sequence dependence and platinum content,” Anti-Cancer Drugs, 1998, 9:525-530.
[cited by applicant]
Cheng, Y. et al., “Dendrimers as drug carriers: applications in different routes of drug administration,” Journal of Pharmaceutical Sciences, Jan. 2008, 97(1):123-143.
[cited by applicant]
Chissov, V.I., ed et al. Oncology. National Guidebook, 2008, pp. 105-111 and 385-393, 38 total pages (with English translation).
[cited by applicant]
Choi, J. et al., “Intraperitoneal immunotherapy for metastatic ovarian carcinoma: Resistance of intratumoral collagen to antibody penetration,” Clin Cancer Res., Mar. 15, 2006, 12(6):1906-1912.
[cited by applicant]
Davidson, B. S. et al., “Collagen matrix cisplatin prevents local tumor growth after margin-positive resection,” J Surg Res., Jun. 1995, 58(6):618-624.
[cited by applicant]
Dimeco, F. et al., “Local delivery of mitoxantrone for the treatment of malignant brain tumors in rats,” J Neurosurg. Nov. 2002, 97(5):1173-1178.
[cited by applicant]
Duvillard, C. et al., “EDTA enhances the antitumor efficacy of intratumoral cisplatin in s.c. grafted rat colon tumors,” Anticancer Drugs. Mar. 2004, 15(3):295-299.
[cited by applicant]
Duvillard, C. et al., “Epinephrine enhances penetration and anti-cancer activity of local cisplatin on rat sub-cutaneous and peritoneal tumors,” Int J Cancer. May 31, 1999, 81(5):779-784.
[cited by applicant]
Duvillard, C. et al., “Phase 2 study of intratumoral cisplatin and epinephrine treatment for locally recurrent head and neck tumors,” Ann Otol Rhinol Laryngol., Mar. 2004, 113(3 Pt 1):229-233.
[cited by applicant]
Elvin, P. et al., “Anti-tumour activity of novel adducts of ascorbic acid with aldehydes,” Eur J Cancer Clin Oncol., Jul. 1981, 17(7):759-765.
[cited by applicant]
Engelmann, K. et al., “CT-guided percutaneous intratumoral chemotherapy with a novel cisplatin/epinephrine injectable gel for the treatment of inoperable malignant liver tumors,” Rofo., Dec. 2000, 172(12):1020-1027 (Eng…
[cited by applicant]
Esquis, P. et al., “High intra-abdominal pressure enhances the penetration and antitumor effect of intraperitoneal cisplatin on experimental peritoneal carcinomatosis,” Ann Surg., Jul. 2006, 244(1):106-112.
[cited by applicant]
Ewend, M. G. et al., “Local delivery of chemotherapy prolongs survival in experimental brain metastases from breast carcinoma,” Neurosurgery, Nov. 1998, 43(5):1185-1193.
[cited by applicant]
Favoulet, P. et al., “Pre-clinical study of the epinephrine-cisplatin association for the treatment of intraperitoneal carcinomatosis,” Eur J Surg Oncol., Feb. 2001, 27(1):59-64.
[cited by applicant]
Flessner, M. F. et al., “Resistance of tumor interstitial pressure to the penetration of intraperitoneally delivered antibodies into metastatic ovarian tumors,” Clin Cancer Res. Apr. 15, 2005, 11(8):3117-3125.
[cited by applicant]
Gondal, J. A. et al., “Comparative pharmacological, toxicological and antitumoral evaluation of free and liposome-encapsulated cisplatin in rodents,” Eur. J Cancer, 1993, 29A(11):1536-1542.
[cited by applicant]
González-Moreno, S. et al., “Hyperthermic intraperitoneal chemotherapy: Rationale and technique,” World J Gastrointest Oncol. Feb. 15, 2010, 2(2):68-75.
[cited by applicant]
Grant, S. C. et al., “Long survival of patients with small cell lung cancer after adjuvant treatment with the anti-idiotypic antibody BEC2 plus bacillus calmette-guerin,” Clin. Cancer Res., 1999, 5:1319-1323.
[cited by applicant]
Gupta, V. et al., “Reduction in cisplatin genotoxicity (micronucleus formation) in non target cells of mice by protransfersome gel formulation used for management of cutaneous squamous cell carcinoma,” Acta Pharmaceutic…
[cited by applicant]
Hamstra, D. A. et al., “Intratumoral injection of BCNU in ethanol (DTI-015) results in enhanced delivery to tumor—a pharmacokinetic study,” J Neuro-Oncol., Jul. 2005, 73(3):225-238.
[cited by applicant]
Holback, H. et al., “Intratumoral drug delivery with nanoparticulate carriers,” Pharm Res. Aug. 2011, 28(8):1819-1830.
[cited by applicant]
Hsu et al., “Determination of 5-fluorouracil in human plasma by high-pressure ion-exchange chromatography,” Ann. Clin. Biochem. 1980, 11:272-276.
[cited by applicant]
Huang, X. et al, “Cisplatin pretreatment enhances anti-tumor activity of cytokine-induced killer cells,” World Journal of Gastroenterology, Jul. 2011, 17(25):3002-3011.
[cited by applicant]
Hu-Lieskovan, S. et al., “Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic ewing's sarcoma,” Cancer Res., 2005, 65:898…
[cited by applicant]
Hwang, T. L. et al., “Permeation enhancer-containing water-in-oil nanoemulsions as carriers for intravesical cisplatin delivery,” Pharmaceutical Research, Oct. 2009, 26(10):2314-2323.
[cited by applicant]
Iinuma, H. et al., “Intracellular targeting therapy of cisplatin-encapsulated transferrin-polyethylene glycol liposome on peritoneal dissemination of gastric cancer,” Int J Cancer., May 1, 2002, 99(1):130-137.
[cited by applicant]
Ikeguchi, M. et al., “Cisplatin combined with prostaglandin E1 chemotherapy in rat peritoneal carcinomatosis,” Int J Cancer. Nov. 1, 2000, 88(3):474-478.
[cited by applicant]
Infante, et al. “Amino acid-based surfactants,” C. R. Chimie, 2004, 7:583-592.
[cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2013/059841, mailed Dec. 17, 2013, 8 pages.
[cited by applicant]
Javadzadeh, Y. et al., “Enhancing percutaneous delivery of methotrexate using different types of surfactants,” Colloids and Surfaces B: Biointerfaces, Feb. 1, 2011, 82(2):422-426.
[cited by applicant]
Koizumi, W. et al., “S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial,” Lancet Oncol. Mar. 2008, 9(3):215-221. Epub Feb. 20, 2008.
[cited by applicant]
Kumagai, S. et al., “Improvement of intraperitoneal chemotherapy for rat ovarian cancer using cisplatin-containing microspheres,” Japan J Cancer Res., Apr. 1996, 87(4):412-417.
[cited by applicant]
Landrito, J. E. et al., “Effects of intralesional injection of cisplatin dissolved in urografin and lipiodol on Ehrlich ascites tumor and normal tissues of CD-1 mice,” Cancer Chemother Pharmacol. 1994, 34(4):323-330.
[cited by applicant]
Leonetti, C. et al., “Increase of cisplatin sensitivity by c-myc antisense oligodeoxynucleotides in a human metastatic melanoma inherently resistant to cisplatin,” Clin Cancer Res., Sep. 1999, 5(9):2588-2595.
[cited by applicant]
“Lesion,” Definition of Lesion by Medical Dictionary, Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition (2003) by Saunders, an imprint of Elsevier, Inc., 5 pages.
[cited by applicant]
Leung, T. W. T. et al., “Phase II study of the efficacy and safety of cisplatin-epinephrine injectable gel administered to patients with unresectable hepatocellular carcinoma,” J Clin Oncol., Feb. 15, 2003, 21(4):652-65…
[cited by applicant]
Li, X. et al., “Superior antitumor efficiency of cisplatin-loaded nanoparticles by intratumoral delivery with decreased tumor metabolism rate,” European Journal of Pharmaceutics and Biopharmaceutics, 2008, 70:726-734.
[cited by applicant]
Liu, Y. et al., “Differential cytostatic effect of sodium salicylate in human colorectal cancers using an individualized histoculture system,” Cancer Chemother Pharmacol., Jun. 2002, 49(6):473-478. Epub Apr. 24, 2002.
[cited by applicant]
Liu, Z. et al., “Delivery of an anticancer drug and a chemosensitizer to murine breast sarcoma by intratumoral injection of sulfopropyl dextran microspheres,” Journal of Pharmacy and Pharmacology 2003, 55:1063-1073.
[cited by applicant]
Los, G. et al., “Anti-tumor effect of cisplatin, carboplatin, mitoxantrone, and doxorubicin on peritoneal tumor growth after intraperitoneal and intravenous chemotherapy: a comparative study,” Sel Cancer Ther., 1990, 6(…
[cited by applicant]
Los, G. et al., “Antitumour response and nephrotoxicity following intraperitoneal administration of a slow release formulation of cisplatin to rats bearing cancers restricted to the peritoneal cavity,” Br J Cancer. Jul.…
[cited by applicant]
Los, G. et al., “Direct diffusion of cis-diamminedichloroplatinum(II) in intraperitoneal rat tumors after intraperitoneal chemotherapy: a comparison with systemic chemotherapy,” Cancer Res., Jun. 15, 1989, 49(12):3380-3…
[cited by applicant]
Los, G. et al., “Platinum distribution in intraperitoneal tumors after intraperitoneal cisplatin treatment,” Cancer Chemother Pharmacol. 1990, 25(6):389-394.
[cited by applicant]
Los, G. et al., “The use of oxaliplatin versus cisplatin in intraperitoneal chemotherapy in cancers restricted to the peritoneal cavity in the rat,” Cancer Lett., May 30, 1990, 51(2):109-117.
[cited by applicant]
Malhotra, H. et al., “Cisplatin/epinephrine injectable gel,” Drugs & Aging, 2001, 18(10):787-793.
[cited by applicant]
Malik, N. et al., “Dendrimer-platinate: a novel approach to cancer chemotherapy,” Anticancer Drugs, Sep. 1999; 10(8):767-776 (Abstract).
[cited by applicant]
Markman, M., “Intraperitoneal antineoplastic agents for tumors principally confined to the peritoneal cavity,” Cancer Treatment Reviews, Dec. 1986, 13(4):219-242.
[cited by applicant]
Masunaga, S. et al., “Enhancement of cisplatin sensitivity of quiescent cells in solid tumors by combined treatment with tirapazamine and low-temperature hyperthermia,” Radiat Med., Nov.-Dec. 1998, 16(6):441-448.
[cited by applicant]
Menjoge, A. R. et al., “Transport and biodistribution of dendrimers across human fetal membranes: Implications for intravaginal administration of dendrimer-drug conjugates,” Biomaterials, 2010, 31:5007-5021.
[cited by applicant]
Mohan, P. et al., “Doxorubicin as a molecular nanotheranostic agent: effect of doxorubicin encapsulation in micelles or nanoemulsions on the ultrasound-mediated intracellular delivery and nuclear trafficking,” Mol Pharm…
[cited by applicant]
Mok, T. S. K. et al., “Pharmacokinetic study of intralesional cisplatin for the treatment of hepatocellular carcinoma,” Cancer, Jun. 15, 2001, 91(12):2369-2377.
[cited by applicant]
Molucon-Chabrot, C. et al., “Feasibility of using intraperitoneal epinephrine and cisplatin in patients with advanced peritoneal carcinomatosis,” Anti-Cancer Drugs, Nov. 2006, 17(10):1211-1217.
[cited by applicant]
Monga, S. P. et al., “Intratumoral therapy of cisplatin/epinephrine injectable gel for palliation in patients with obstructive esophageal cancer,” Am J Clin Oncol., Aug. 2000, 23(4):386-392.
[cited by applicant]
Motlekar, N. A. et al., “Evaluation of the Oral Bioavailability of Low Molecular Weight Heparin Formulated With Glycyrrhetinic Acid as Permeation Enhancer,” Drug Dev Res., Feb. 2006, 67(2):166-174.
[cited by applicant]
Namur, J. et al., “Embolization of hepatocellular carcinoma with drug-eluting beads: doxorubicin tissue concentration and distribution in patient liver explants,” J Hepatol., Dec. 2011, 55(6):1332-1338.
[cited by applicant]
National Cancer Institute, Dictionary of Cancer Terms, “Solid Tumor,” WayBack Machine [Online], http://www.cancer.gov/dictionary?CdrID=45301, Mar. 27, 2011, 1 page.
[cited by applicant]
National Cancer Institute, Understanding Cancer Series: Cancer, “Slide 9: Malignant versus Benign Tumors,” WayBack Machine [Online], http://www.cancer.gov/cancertopics/understandingcancer/cancer/page9, Mar. 28, 2011, 2 …
[cited by applicant]
Newman, M. S. et al., “Comparative pharmacokinetics, tissue distribution, and therapeutic effectiveness of cisplatin encapsulated in long-circulating, pegylated liposomes (SPI-077) in tumor-bearing mice,” Cancer Chemoth…
[cited by applicant]
Okamoto, H. et al., “Local and systemic delivery of high-molecular weight drugs by powder inhalation,” The Pharmaceutical Society of Japan, Apr. 2007, 127(4):643-653.
[cited by applicant]
Okuyama, S. et al., “Intratumoral doxycycline for skin metastases of human malignancies,” Tohoku J Exp Med., Feb. 1987, 151(2):241-244.
[cited by applicant]
Onier, N. et al., “Cure of colon cancer metastasis in rats with the new lipid A OM 174. Apoptosis of tumor cells and immunization of rats,” Clin Exp Metastasis. Jun. 1999, 17(4):299-306.
[cited by applicant]
Oratz, R. et al., “Intratumoral cisplatin/adrenaline injectable gel for the treatment of patients with cutaneous and soft tissue metastases of malignant melanoma,” Melanoma Research, 2003, 13(1):59-66.
[cited by applicant]
Ozols, R. F. et al., “Chemotherapy For Murine Ovarian Cancer: A Rationale For Ip Therapy With Adriamycin,” Cancer Treat Rep., Feb. 1979, 63(2):269-273.
[cited by applicant]
Peaston, A. et al., “Treatment of superficial tumours on horses with dimethyl sulfoxide and cisplatin,” Aust Vet J., Feb. 1995, 72(2):76-77.
[cited by applicant]
Poirson-Bichat, F. et al., “Methionine depletion enhances the antitumoral efficacy of cytotoxic agents in drug-resistant human tumor xenografts,” Clin Cancer Res., Feb. 2000, 6(2):643-653.
[cited by applicant]
Ramesh, G. et al., “Salicylate reduces cisplatin nephrotoxicity by inhibition of tumor necrosis factor-alpha,” Kidney Int., Feb. 2004, 65(2):490-499.
[cited by applicant]
Rossi, C. R. et al., “Pharmacokinetics of intraperitoneal cisplatin and doxorubicin,” Surg Oncol Clin N Am., Jul. 2003, 12(3):781-794.
[cited by applicant]
Saad, M. et al., “Co-delivery of siRNA and an anticancer drug for treatment of multidrug-resistant cancer,” Nanomedicine (Lond)., Dec. 2008, 3(6):761-776.
[cited by applicant]
Sawyer, A. J. et al., “Convection-enhanced delivery of camptothecin-loaded polymer nanoparticles for treatment of intracranial tumors,” Drug Deliv Transl Res., Feb. 1, 2011, 1(1):34-42.
[cited by applicant]
Settelen, N. et al., “Controlled plasmid gene transfer to murine renal carcinoma by hexadecylphosphocholine,” Journal of Controlled Release, Jan. 2004, 94(1):237-244.
[cited by applicant]
Shen, Z. et al., “Intravesical treatments of bladder cancer: review,” Pharmaceutical Research, Jul. 2008, 25(7):1500-1510.
[cited by applicant]
Soloway, A. H. et al., “Penetration of Brain and Brain Tumors by Intravascular Injection of Alkylating Agents,” J Med Pharm Chem., Nov. 1962, 91:1371-1376.
[cited by applicant]
Speyer, J. L. et al., “Intraperitoneal carboplatin: rationale and experience,” Semin Oncol. Feb. 1992, 19(1 Suppl 2):107-113.
[cited by applicant]
Stavrovskaya A.A. et al., “The Effect of Non-ionic Detergent Tween 80 on Colcemid-Resistant Transformed Mouse Cells In Vitro,” Int. J. Cancer, 1975, 15:665-672.
[cited by applicant]
Supplementary European Search Report for European Application No. 13838639.6, mailed Apr. 1, 2016, 11 pages.
[cited by applicant]
Suzuki, K. et al., “A new drug delivery system for local cancer chemotherapy using cisplatin and chitin,” Anticancer Res., Mar.-Apr. 1995, 15(2):423-426.
[cited by applicant]
Tamura, T. et al., “Anti-tumor effect of intraperitoneal administration of cisplatin-loaded microspheres to human tumor xenografted nude mice,” J Control Release, Apr. 23, 2002, 80(1-3):295-307.
[cited by applicant]
Tao, W. et al., “Distribution of 5-fluorouracil in plasma and pancreatic tissue of rats during the regional arterial infusion chemotherapy,” Zhongguo Yi Xue Ke Xue Yuan Xue Bao., Oct. 1999, 21(5):390-394 (English Abstra…
[cited by applicant]
Théon, A. P. et al., “Long-term outcome associated with intratumoral chemotherapy with cisplatin for cutaneous tumors in equidae,” 573 cases (1995-2004). J Am Vet Med Assoc. May 15, 2007; 230(10):1506-1513.
[cited by applicant]
Tong, A. W. et al., “Intratumoral injection of INGN 241, a nonreplicating adenovector expressing the melanoma-differentiation associated gene-7 (mda-7/IL24): biologic outcome in advanced cancer patients,” Mol Ther., Jan…
[cited by applicant]
Toomey, P. et al., “Intralesional injection of rose bengal induces a systemic tumor-specific immune response in murine models of melanoma and breast cancer,” PLOSOne [Online at www.plosone.org], Jul. 2013, 8(7):e68561, …
[cited by applicant]
Tyler, B. et al., “A thermal gel depot for local delivery of paclitaxel to treat experimental brain tumors in rats,” J Neurosurg., Aug. 2010, 113(2):210-217.
[cited by applicant]
Tyler, B. M. et al., “Delayed onset of paresis in rats with experimental intramedullary spinal cord gliosarcoma following intratumoral administration of the paclitaxel delivery system,” OncoGel., J Neurosurg Spine, Jan.…
[cited by applicant]
Tzafriri, A. R. et al., “Diffusion-limited binding explains binary dose response for local arterial and tumour drug delivery,” Cell Prolif. Jun. 2009, 42(3):348-363.
[cited by applicant]
Van Putte, B. P. et al., “Combination chemotherapy with gemcitabine with isolated lung perfusion for the treatment of pulmonary metastases,” J Thorac Cardiovasc Surg., Jul. 2005, 130(1):125-130.
[cited by applicant]
Vincent, L. et al., “Efficacy of dendrimer-mediated angiostatin and TIMP-2 gene delivery on inhibition of tumor growth and angiogenesis: in vitro and in vivo studies,” Int. J. Cancer, Jun. 2003, 105(3):419-429.
[cited by applicant]
Vogl, T. J. et al., “CT-guided intratumoural administration of cisplatin/epinephrine gel for treatment of malignant liver tumours,” Br J Cancer., Feb. 12, 2002, 86(4):524-529.
[cited by applicant]
Weinberg, B. D. et al., “Antitumor efficacy and local distribution of doxorubicin via intratumoral delivery from polymer millirods,” J Biomed Mater Res A., Apr. 2007, 81(1):161-170.
[cited by applicant]
Weinberg, B. D. et al., “Model simulation and experimental validation of intratumoral chemotherapy using multiple polymer implants,” Med Biol Eng Comput., Oct. 2008, 46(10):1039-1049.
[cited by applicant]
Werner, J. A. et al., “A phase III placebo-controlled study in advanced head and neck cancer using intratumoural cisplatin/epinephrine gel,” Br J Cancer., Oct. 21, 2002, 87(9):938-944.
[cited by applicant]
Wolinsky, J. B. et al., “Local drug delivery strategies for cancer treatment: gels, nanoparticles, polymeric films, rods, and wafers,” J Control Release., Apr. 10, 2012, 159(1):14-26. Epub Dec. 1, 2011.
[cited by applicant]
Wong, S-F., “Cetuximab: An Epidermal Growth Factor Receptor Monoclonal Antibody for the Treatment of Colorectal Cancer,” Clinical Therapeutics, 2005, 27(6):684-694.
[cited by applicant]
Yoshida, D. et al., “Dermatopharmacokinetics of salicylate following topical injection in rats: effect of osmotic pressure and injection volume on salicylate disposition,” Int J Pharm., Jun. 7, 2007, 337(1-2):142-147.
[cited by applicant]
Zahedi, P. et al., “An injectable depot system for sustained intraperitoneal chemotherapy of ovarian cancer results in favorable drug distribution at the whole body, peritoneal and intratumoral levels,” J Control Releas…
[cited by applicant]
Zamboni, W. C. et al., “Inter- and intratumoral disposition of platinum in solid tumors after administration of cisplatin,” Clin Cancer Res., Sep. 2002, 8(9):2992-2999.
[cited by applicant]
Zheng, J. L. et al., “Distribution of 5-FU in rat plasma and liver tissue after local 5-FU infusion,” J South Med University, May 2008, 28(5):823-827 (English Abstract).
[cited by applicant]
Zhong, H. et al., “Low-Dose Paclitaxel Prior to Intratumoral Dendritic Cell Vaccine Modulates Intratumoral Cytokine Network and Lung Cancer Growth,” Clin. Cancer Res., Sep. 2007, 13(18):5455-5462.
[cited by applicant]