Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer

PLoS ONE

Volumn 7, Issue 1, 2012, Pages

  Monti, Daniel A ^a   Mitchell, Edith ^b   Bazzan, Anthony J ^a   Littman, Susan ^b   Zabrecky, George ^a   Yeo, Charles J ^a   Pillai, Madhaven V ^b   Newberg, Andrew B ^a   Deshmukh, Sandeep ^b   Levine, Mark ^c  

^a THOMAS JEFFERSON UNIVERSITY   (United States)

^b THOMAS JEFFERSON UNIVERSITY   (United States)

^c NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ASCORBIC ACID; ERLOTINIB; GEMCITABINE; ANTINEOPLASTIC AGENT; DEOXYCYTIDINE; DRUG DERIVATIVE; QUINAZOLINE DERIVATIVE;

ADULT; AGED; ARTICLE; ASCITES; CANCER PATIENT; CANCER STAGING; CLINICAL ARTICLE; COHORT ANALYSIS; CONJUNCTIVITIS; CONTROLLED STUDY; DEATH; DIZZINESS; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG FATALITY; DRUG SAFETY; FEMALE; FOLLOW UP; GASTROINTESTINAL SYMPTOM; HUMAN; ILEUS; LUNG EMBOLISM; MALE; METASTASIS; NAUSEA; NEUTROPHIL COUNT; OPEN STUDY; OVERALL SURVIVAL; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL; PROGRESSION FREE SURVIVAL; SIDE EFFECT; SINGLE DRUG DOSE; THROMBOCYTE COUNT; TREATMENT OUTCOME; URINARY TRACT INFECTION; CHEMICALLY INDUCED DISORDER; CLINICAL TRIAL; DOSE RESPONSE; DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; MIDDLE AGED; PANCREAS TUMOR; PATHOLOGY;

AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; ASCORBIC ACID; DEOXYCYTIDINE; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; INFUSIONS, INTRAVENOUS; MALE; MIDDLE AGED; NEOPLASM METASTASIS; NEOPLASM STAGING; PANCREATIC NEOPLASMS; PULMONARY EMBOLISM; QUINAZOLINES; TREATMENT OUTCOME;

EID: 84855858767     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0029794     Document Type: Article

References (34)

1. Yeo CJ, Cameron JL, Sohn TA, Lillemoe KD, Pitt HA, et al. (1997) Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s: pathology, complications, and outcomes. Ann Surg 226: 248-257.
2. Van Cutsem E, van de Velde H, Karasek P, Oettle H, Vervenne WL, et al. (2004) Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol 22 (8): 1430-1438.
3. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, et al. (2007) Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25 (15): 1960-1966.
4. Reni M, Cordio S, Milandri C, Passoni P, Bonetto E, et al. (2005) Gemcitabine versus cisplatin, epirubicin, fluorouracil, and gemcitabine in advanced pancreatic cancer: A randomized controlled multicentre phase III trial. Lancet Oncol 6: 369-376.
5. Padayatty SJ, Sun AY, Chen Q, Espey MG, Drisko J, et al. (2010) Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One 5 (7): e11414.
6. Cameron E, Pauling L, (1976) Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A 73 (10): 3685-3689.
7. Cameron E, Pauling L, (1978) Supplemental ascorbate in the supportive treatment of cancer: reevaluation of prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A 75 (9): 4538-4542.
8. Creagan ET, Moertel CG, O'Fallon JR, Schutt AJ, O'Connell MJ, et al. (1979) Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patient with advanced cancer. A controlled trial. New Engl J Med 301: 687-690.
9. Moertel CG, Fleming TR, Creagan ET, Rubin J, O'Connell MJ, et al. (1985) High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-0blind comparison. N Engl J Med 312: 137-141.
10. Wittes RE, (1985) Vitamin C and cancer. N Engl J Med 312 (3): 178-179.
11. Coulter ID, Hardy ML, Morton SC, Hilton LG, Tu W, et al. (2006) Antioxidants vitamin C and vitamin E for the prevention and treatment of cancer. J Gen Intern Med 21 (7): 735-744.
12. Padayatty SJ, Levine M, (2000) Reevaluation of ascorbate in cancer treatment: emerging evidence, open minds and serendipity. J Am Coll Nutr 19 (4): 423-425.
13. Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, et al. (2004) Vitamin C pharmacokinetics: Implications for oral and intravenous use. Ann Intern Med 140: 533-537.
14. Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, et al. (2005) Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci U S A 102 (38): 13604-13609.
15. Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, et al. (2008) Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci U S A 105: 11105-11109.
16. Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, et al. (1996) Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci U S A 93: 3704-3709.
17. Levine M, Wang Y, Padayatty SJ, Morrow J, (2001) A new recommended dietary allowance of vitamin C for healthy young women. Proc Natl Acad Sci U S A 2001; 98 (17): 9842-9846.
18. Hoffer LJ, Levine M, Assouline S, Melnychuk D, Padayatty SJ, et al. (2008) Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann Oncol 19 (11): 1969-1974.
19. Chen Q, Espey MG, Sun AY, Lee JH, Krishna MC, et al. (2007) Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc Natl Acad Sci U S A 104 (21): 8749-8754.
20. Espey MG, Chen P, Chalmers B, Drisko J, Sun AY, et al. (2011) Pharmacologic ascorbate synergizes with gemcitabine in preclinical models of pancreatic cancer. Free Radic Biol Med 50 (11): 1610-1619.
21. Schulz KF, Altman DG, Moher D, for the CONSORT Group. (2010) CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. Trials 11: 32.
22. Jackson P, Loughrey CM, Lightbody JH, McNamee PT, Young IS, et al. (1995) Effect of hemodialysis on total antioxidant capacity and serum antioxidants in patients with chronic renal failure. Clin Chem 41 (8 Pt 1): 1135-1138.
23. Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version 3.0, DCTD, NCI, NIH, DHHS. March 31, 2003, Publish date: August 9, 2006 Available:http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf Accessed 2011 November 15.
24. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, et al. (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45 (2): 228-247.
25. Shaib W, Deng Y, Zilterman D, Lundberg B, Saif MW, (2010) Assessing risk and mortality of venous thromboembolism in pancreatic cancer patients. Anticancer Res 30 (10): 4261-4264.
26. Feliu J, Borrega P, León A, López-Gómez L, López M, et al. (2011) Phase II study of a fixed dose-rate infusion of gemcitabine associated with erlotinib in advanced pancreatic cancer. Cancer Chemother Pharmacol 67 (1): 215-221.
27. Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, et al. (2009) Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 27 (33): 5513-5518.
28. Ardavanis A, Kountourakis P, Karagiannis A, Doufexis D, Tzovaras AA, et al. (2009) Biweekly gemcitabine (GEM) in combination with erlotinib (ERL): an active and convenient regimen for advanced pancreatic cancer. Anticancer Res 29 (12): 5211-5217.
29. Heinemann V, Quietzsch D, Gieseler F, Gonnermann M, Schönekäs H, et al. (2006) Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol 24: 3946-3952.
30. Stathopoulos GP, Syrigos K, Aravantinos G, Polyzos A, Papakotoulas P, et al. (2006) A multicenter phase III trial comparing irinotecan-gemcitabine (IG) with gemcitabine (G) monotherapy as first line treatment in patients with locally advanced or metastatic pancreatic cancer. Br J Cancer 95: 587-592.
31. Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, et al. (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial. J Clin Oncol 15: 2403-2413.
32. Drisko JA, Chapman J, Hunter VJ, (2003) The use of antioxidants with first-line chemotherapy in two cases of ovarian cancer. J Amer Coll Nutr 22: 118-23.
33. Padayatty SJ, Riordan HD, Hewitt SM, Katz A, Hoffer LJ, et al. (2006) Intravenous vitamin C as cancer treatment: Three cases. Can Med Assoc J 174: 937-942.
34. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, et al. (2007) Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25 (15): 1960-1966.