The host response to cancer virotherapy

Current Opinion in Molecular Therapeutics

Volumn 10, Issue 1, 2008, Pages 38-45

  Chiocca, E A ^a  

^a THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER   (United States)

Author keywords

Angiogenesis; Clinical trial; Cyclophosphamide; Gene therapy; Innate immunity; Oncolytic virus

Indexed keywords

CYCLOPHOSPHAMIDE; ONCOLYTIC VIRUS;

DRUG EFFICACY; HERPES SIMPLEX VIRUS 1; IN VITRO STUDY; REVIEW; TUMOR CELL; VIROTHERAPY; VIRUS INFECTION; VIRUS REPLICATION;

ANIMALS; HUMANS; IMMUNITY; NEOPLASMS; ONCOLYTIC VIROTHERAPY;

EID: 38649103832     PISSN: 14648431     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (88)

1. Chiocca EA: Oncolytic viruses. Nat Rev Cancer (2002) 2(12):938-950.
2. Parato KA, Senger D, Forsyth PA, Bell JC: Recent progress in the battle between oncolytic viruses and tumours. Nat Rev Cancer (2005) 5(12):965-976.
3. Martuza RL, Malick A, Markert JM, Ruffner KL, Coen DM: Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science (1991) 252(5007):854-856.
4. Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M, Ng L, Nye JA, Sampson-Johannes A, Fattaey A, McCormick F: An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science (1996) 274(5286):373-376.
5. O'Shea CC, Johnson L, Bagus B, Choi S, Nicholas C, Shen A, Boyle L, Pandey K, Soria C, Kunich J, Shen Y et al: Late viral RNA export, rather than p53 inactivation, determines ONYX-015 tumor selectivity. Cancer Cell (2004) 6(6):611-623.
6. O'Shea CC, Soria C, Bagus B, McCormick F: Heat shock phenocopies E1B-55K late functions and selectively sensitizes refractory tumor cells to ONYX-015 oncolytic viral therapy. Cancer Cell (2005) 8(1):61-74.
7. Markert JM, Medlock MD, Rabkin SD, Gillespie GY, Todo T, Hunter WD, Palmer CA, Feigenbaum F, Tornatore C, Tufaro F, Martuza RL: Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: Results of a phase I trial. Gene Ther (2000) 7(10):867-874.
8. Chiocca EA, Abbed KM, Tatter S, Louis DN, Hochberg FH, Barker F, Kracher J, Grossman SA, Fisher JD, Carson K, Rosenblum M et al: A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting. Mol Ther (2004) 10(5):958-966.
9. Laurie SA, Bell JC, Atkins HL, Roach J, Bamat MK, O'Neil JD, Roberts MS, Groene WS, Lorence RM: A phase 1 clinical study of intravenous administration of PV701, an oncolytic virus, using two-step desensitization. Clin Cancer Res (2006) 12(8):2555-2562. • This study demonstrated that OVs can be delivered intravenously and that human 'flu-like' symptoms can be reduced by desensitization.
10. Pecora AL, Rizvi N, Cohen GI, Meropol NJ, Sterman D, Marshall JL, Goldberg S, Gross P, O'Neil JD, Groene WS, Roberts MS et al: Phase I trial of intravenous administration of PV701, an oncolytic virus, in patients with advanced solid cancers. J Clin Oncol (2002) 20(9):2251- 2266.
11. Hecht JR, Bedford R, Abbruzzese JL, Lahoti S, Reid TR, Soetikno RM, Kirn DH, Freeman SM: A phase I/II trial of intratumoral endoscopic ultrasound injection of ONYX-015 with intravenous gemcitabine in unresectable pancreatic carcinoma. Clin Cancer Res (2003) 9(2):555-561.
12. Nemunaitis J, Ganly I, Khuri F, Arseneau J, Kuhn J, McCarty T, Landers S, Maples P, Romel L, Randlev B, Reid T et al: Selective replication and oncolysis in p53 mutant tumors with ONYX-015, an E1B-55kD gene-deleted adenovirus, in patients with advanced head and neck cancer: A phase II trial. Cancer Res (2000) 60(22):6359-6366.
13. Reid T, Galanis E, Abbruzzese J, Sze D, Andrews J, Romel L, Hatfield M, Rubin J, Kirn D: Intra-arterial administration of a replication-selective adenovirus (dl1520) in patients with colorectal carcinoma metastatic to the liver: A phase I trial. Gene Ther (2001) 8(21):1618-1626.
14. Reid T, Galanis E, Abbruzzese J, Sze D, Wein LM, Andrews J, Randlev B, Heise C, Uprichard M, Hatfield M, Rome L et al: Hepatic arterial infusion of a replication-selective oncolytic adenovirus (dl1520): Phase II viral, immunologic, and clinical endpoints. Cancer Res (2002) 62(21):6070-6079.
15. Harrow S, Papanastassiou V, Harland J, Mabbs R, Petty R, Fraser M, Hadley D, Patterson J, Brown SM, Rampling R: HSV1716 injection into the brain adjacent to tumour following surgical resection of high-grade glioma: Safety data and long-term survival. Gene Ther (2004) 11(22):1648- 1658.
16. Rampling R, Cruickshank G, Papanastassiou V, Nicoll J, Hadley D, Brennan D, Petty R, MacLean A, Harland J, McKie E, Mabbs R, Brown M: Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma. Gene Ther (2000) 7(10):859-866.
17. Khuri FR, Nemunaitis J, Ganly I, Arseneau J, Tannock IF, Romel L, Gore M, Ironside J, MacDougall RH, Heise C, Randlev B et al: A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med (2000) 6(8):879-885. •• The first clinical trial to demonstrate the efficacy of OVs, albeit in combination with chemotherapy.
18. Waehler R, Russell SJ, Curiel DT: Engineering targeted viral vectors for gene therapy. Nat Rev Genet (2007) 8(8):573-587.
19. Kamiyama H, Zhou G, Roizman B: Herpes simplex virus 1 recombinant virions exhibiting the amino terminal fragment of urokinase-type plasminogen activator can enter cells via the cognate receptor. Gene Ther (2006) 13(7):621-629.
20. Paraskevakou G, Allen C, Nakamura T, Zollman P, James CD, Peng KW, Schroeder M, Russell SJ, Galanis E: Epidermal growth factor receptor (EGFR)-retargeted measles virus strains effectively target EGFR- or EGFRvIII expressing gliomas. Mol Ther (2007) 15(4):677-686. • An example of retargeting the tropism of an OV toward a cell surface receptor that was highly expressed in gliomas.
21. Kasahara N, Dozy AM, Kan YW: Tissue-specific targeting of retroviral vectors through ligand-receptor interactions. Science (1994) 266(5189):1373-1376.
22. Chung RY, Saeki Y, Chiocca EA: B-myb promoter retargeting of herpes simplex virus γ34.5 gene-mediated virulence toward tumor and cycling cells. J Virol (1999) 73(9):7556- 7564.
23. Farassati F, Yang AD, Lee PW: Oncogenes in Ras signalling pathway dictate host-cell permissiveness to herpes simplex virus 1. Nat Cell Biol (2001) 3(8):745-750.
24. Kambara H, Okano H, Chiocca EA, Saeki Y: An oncolytic HSV-1 mutant expressing ICP34.5 under control of a nestin promoter increases survival of animals even when symptomatic from a brain tumor. Cancer Res (2005) 65(7):2832-2839. • An example of a powerful OV that exhibited specifically targeted replication to nestin-expressing glioma tumors.
25. Balachandran S, Barber GN: Defective translational control facilitates vesicular stomatitis virus oncolysis. Cancer Cell (2004) 5(1):51-65.
26. Stojdl DF, Lichty BD, tenOever BR, Paterson JM, Power AT, Knowles S, Marius R, Reynard J, Poliquin L, Atkins H, Brown EG et al: VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents. Cancer Cell (2003) 4(4):263-275. •• This study showed that defects in tumor cell innate responses may provide targets for some OVs.
27. Berns K, Horlings HM, Hennessy BT, Madiredjo M, Hijmans EM, Beelen K, Linn SC, Gonzalez-Angulo AM, Stemke-Hale K, Hauptmann M, Beijersbergeb RL et al: A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell (2007) 12(4):395-402.
28. Boviatsis EJ, Chase M, Wei MX, Tamiya T, Hurford RK Jr, Kowall NW, Tepper RI, Breakefield XO, Chiocca EA: Gene transfer into experimental brain tumors mediated by adenovirus, herpes simplex virus, and retrovirus vectors. Hum Gene Ther (1994) 5(2):183-191.
29. Chase M, Chung RY, Chiocca EA: An oncolytic viral mutant that delivers the CYP2B1 transgene and augments cyclophosphamide chemotherapy. Nat Biotechnol (1998) 16(5):444-448.
30. Hiraoka K, Kimura T, Logg CR, Tai CK, Haga K, Lawson GW, Kasahara N: Therapeutic efficacy of replication-competent retrovirus vector-mediated suicide gene therapy in a multifocal colorectal cancer metastasis model. Cancer Res (2007) 67(11):5345-5353.
31. Hellums EK, Markert JM, Parker JN, He B, Perbal B, Roizman B, Whitley RJ, Langford CP, Bharara S, Gillespie GY: Increased efficacy of an interleukin-12-secreting herpes simplex virus in a syngeneic intracranial murine glioma model. Neuro Oncol (2005) 7(3):213-224.
32. Parker JN, Gillespie GY, Love CE, Randall S, Whitley RJ, Markert JM: Engineered herpes simplex virus expressing IL-12 in the treatment of experimental murine brain tumors. Proc Natl Acad Sci USA (2000) 97(5):2208-2213.
33. Dingli D, Peng KW, Harvey ME, Greipp PR, O'Connor MK, Cattaneo R, Morris JC, Russell SJ: Image-guided radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal sodium iodide symporter. Blood (2004) 103(5):1641-1646.
34. Hasegawa K, Pham L, O'Connor MK, Federspiel MJ, Russell SJ, Peng KW: Dual therapy of ovarian cancer using measles viruses expressing carcinoembryonic antigen and sodium iodide symporter. Clin Cancer Res (2006) 12(6):1868-1875.
35. Wakimoto H, Johnson PR, Knipe DM, Chiocca EA: Effects of innate immunity on herpes simplex virus and its ability to kill tumor cells. Gene Ther (2003) 10(11):983-990.
36. Van Houdt WJ, Wu H, Glasgow JN, Lamfers ML, Dirven CM, Gillespie GY, Curiel DT, Haviv YS: Gene delivery into malignant glioma by infectivity-enhanced adenovirus: In vivo versus in vitro models. Neuro Oncol (2007) 9(3):280-290.
37. Schellingerhout D, Bogdanov A Jr, Marecos E, Spear M, Breakefield X, Weissleder R: Mapping the in vivo distribution of herpes simplex virions. Hum Gene Ther (1998) 9(11):1543-1549.
38. Schellingerhout D, Rainov NG, Breakefield XO, Weissleder R: Quantitation of HSV mass distribution in a rodent brain tumor model. Gene Ther (2000) 7(19):1648-1655.
39. Barnett FH, Rainov NG, Ikeda K, Schuback DE, Elliott P, Kramm CM, Chase M, Qureshi NH, Harsh G, Chiocca EA, Breakefield XO: Selective delivery of herpes virus vectors to experimental brain tumors using RMP-7. Cancer Gene Ther (1999) 6(1):14-20.
40. Nilaver G, Muldoon LL, Kroll RA, Pagel MA, Breakefield XO, Davidson BL, Neuwelt EA: Delivery of herpesvirus and adenovirus to nude rat intracerebral tumors after osmotic blood-brain barrier disruption. Proc Natl Acad Sci USA (1995) 92(21):9829-9833.
41. Ikeda K, Ichikawa T, Wakimoto H, Silver JS, Deisboeck TS, Finkelstein D, Harsh GR, Louis DN, Bartus RT, Hochberg FH, Chiocca EA: Oncolytic virus therapy of multiple tumors in the brain requires suppression of innate and elicited antiviral responses. Nat Med (1999) 5(8):881-887. •• This study brings to the forefront the effects of innate immunity in limiting OV therapy and demonstrated that CPA is an effective enhancer of oncolysis.
42. Ikeda K, Wakimoto H, Ichikawa T, Jhung S, Hochberg FH, Louis DN, Chiocca EA: Complement depletion facilitates the infection of multiple brain tumors by an intravascular, replication-conditional herpes simplex virus mutant. J Virol (2000) 74(10):4765-4775.
43. Wakimoto H, Fulci G, Tyminski E, Chiocca EA: Altered expression of antiviral cytokine mRNAs associated with cyclophosphamide's enhancement of viral oncolysis. Gene Ther (2004) 11(2):214-223.
44. Wakimoto H, Ikeda K, Abe T, Ichikawa T, Hochberg FH, Ezekowitz RA, Pasternack MS, Chiocca EA: The complement response against an oncolytic virus is species-specific in its activation pathways. Mol Ther (2002) 5(3):275-282.
45. Barber GN: VSV-tumor selective replication and protein translation. Oncogene (2005) 24(52):7710-7719.
46. Stojdl DF, Lichty B, Knowles S, Marius R, Atkins H, Sonenberg N, Bell JC: Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nat Med (2000) 6(7):821-825.
47. Breitbach CJ, Paterson JM, Lemay CG, Falls TJ, McGuire A, Parato KA, Stojdl DF, Daneshmand M, Speth K, Kirn D, McCart JA et al: Targeted inflammation during oncolytic virus therapy severely compromises tumor blood flow. Mol Ther (2007) 15(9):1686-1693.
48. Power AT, Wang J, Falls TJ, Paterson JM, Parato KA, Lichty BD, Stojdl DF, Forsyth PA, Atkins H, Bell JC: Carrier cell-based delivery of an oncolytic virus circumvents antiviral immunity. Mol Ther (2007) 15(1):123-130. • This study demonstrated that carrier cells can shield OVs from the immune system.
49. Aghi M, Rabkin SD, Martuza RL: Angiogenic response caused by oncolytic herpes simplex virus-induced reduced thrombospondin expression can be prevented by specific viral mutations or by administering a thrombospondin-derived peptide. Cancer Res (2007) 67(2):440-444. • This study showed that angiogenic responses were a consequence of OV therapy.
50. Friedman A, Tian JP, Fulci G, Chiocca EA, Wang J: Glioma virotherapy: Effects of innate immune suppression and increased viral replication capacity. Cancer Res (2006) 66(4):2314-2319.
51. Fulci G, Breymann L, Gianni D, Kurozomi K, Rhee SS, Yu J, Kaur B, Louis DN, Weissleder R, Caligiuri MA, Chiocca EA: Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses. Proc Natl Acad Sci USA (2006) 103(34):12873-12878. • This study showed that CPA limited mononuclear cell responses to an ongoing OV infection.
52. Fulci G, Dmitrieva N, Gianni D, Fontana EJ, Pan X, Lu Y, Kaufman CS, Kaur B, Lawler SE, Lee RJ, Marsh CB et al: Depletion of peripheral macrophages and brain microglia increases brain tumor titers of oncolytic viruses. Cancer Res (2007) 67(19):9398-9406.
53. Herrlinger U, Kramm CM, Aboody-Guterman KS, Silver JS, Ikeda K, Johnston KM, Pechan PA, Barth RF, Finkelstein D, Chiocca EA, Louis DN, Breakefield XO: Pre-existing herpes simplex virus 1 (HSV-1) immunity decreases, but does not abolish, gene transfer to experimental brain tumors by a HSV-1 vector. Gene Ther (1998) 5(6):809-819.
54. Kurozumi K, Hardcastle J, Yang M, Christoforidis G, Fulci G, Hochberg FH, Weissleder RW, Carson W, Chiocca EA, Kaur B: Effects of tumor microenvironment modulation on the efficacy of oncolytic virus therapy. J Natl Cancer Inst (2007): doi:10.1093/jnci/djm229.
55. Lamfers ML, Fulci G, Gianni D, Tang Y, Kurozumi K, Kaur B, Moeniralm S, Saeki Y, Carette JE, Weissleder R, Vandertop WP et al: Cyclophosphamide increases transgene expression mediated by an oncolytic adenovirus in glioma-bearing mice monitored by bioluminescence imaging. Mol Ther (2006) 14(6):779-788.
56. Hiscott J: Triggering the innate antiviral response through IRF-3 activation. J Biol Chem (2007) 282(21):15325-15329.
57. Uematsu S, Akira S: Toll-like receptors and type I interferons. J Biol Chem (2007) 282(21):15319-15323.
58. Cao W, Bao C, Lowenstein CJ: Inducible nitric oxide synthase expression inhibition by adenovirus E1A. Proc Natl Acad Sci USA (2003) 100(13):7773-7778.
59. Mohr I: Neutralizing innate host defenses to control viral translation in HSV-1 infected cells. Int Rev Immunol (2004) 23 (1-2):199-220.
60. Haralambieva I, Iankov I, Hasegawa K, Harvey M, Russell SJ, Peng KW: Engineering oncolytic measles virus to circumvent the intracellular innate immune response. Mol Ther (2007) 15(3):588-597.
61. Höti N, Chowdhury W, Hsieh JT, Sachs MD, Lupold SE, Rodriguez R: Valproic acid, a histone deacetylase inhibitor, is an antagonist for oncolytic adenoviral gene therapy. Mol Ther (2006) 14(6):768-778.
62. Yu Z, Adusumilli PS, Eisenberg DP, Darr E, Ghossein RA, Li S, Liu S, Singh B, Shah JP, Fong Y, Wong RJ: Nectin-1 expression by squamous cell carcinoma is a predictor of herpes oncolytic sensitivity. Mol Ther (2007) 15(1):103-113.
63. Yu Z, Li S, Huang YY, Fong Y, Wong RJ: Calcium depletion enhances nectin-1 expression and herpes oncolytic therapy of squamous cell carcinoma. Cancer Gene Ther (2007) 14(8):738-747.
64. Miller CR, Buchsbaum DJ, Reynolds PN, Douglas JT, Gillespie GY, Mayo MS, Raben D, Curiel DT: Differential susceptibility of primary and established human glioma cells to adenovirus infection: Targeting via the epidermal growth factor receptor achieves fiber receptor-independent gene transfer. Cancer Res (1998) 58(24):5738-5748.
65. McKee TD, Grandi P, Mok W, Alexandrakis G, Insin N, Zimmer JP, Bawendi MG, Boucher Y, Breakefield XO, Jain RK: Degradation of fibrillar collagen in a human melanoma xenograft improves the efficacy of an oncolytic herpes simplex virus vector. Cancer Res (2006) 66(5):2509-2513. • Collagen in the extracellular tumor matrix provided a barrier to OV propagation.
66. Hay JG: The potential impact of hypoxia on the success of oncolytic virotherapy. Curr Opin Mol Ther (2005) 7(4):353-358.
67. Pipiya T, Sauthoff H, Huang YQ, Chang B, Cheng J, Heitner S, Chen S, Rom WN, Hay JG: Hypoxia reduces adenoviral replication in cancer cells by downregulation of viral protein expression. Gene Ther (2005) 12(11):911-917.
68. Connor JH, Naczki C, Koumenis C, Lyles DS: Replication and cytopathic effect of oncolytic vesicular stomatitis virus in hypoxic tumor cells in vitro and in vivo. J Virol (2004) 78(17):8960-8970.
69. Neuwelt EA, Pagel MA, Dix RD: Delivery of ultraviolet-inactivated 35S-herpesvirus across an osmotically modified blood-brain barrier. J Neurosurg (1991) 74(3):475-479.
70. Liu JY, Wu Y, Zhang XS, Yang JL, Li HL, Mao YQ, Wang Y, Cheng X, Li YQ, Xia JC, Masucci M, Zeng YX: Single administration of low dose cyclophosphamide augments the antitumor effect of dendritic cell vaccine. Cancer Immunol Immunother (2007) 56(10):1597-1604.
71. Li H, Zeng Z, Fu X, Zhang X: Coadministration of a herpes simplex virus-2 based oncolytic virus and cyclophosphamide produces a synergistic antitumor effect and enhances tumor-specific immune responses. Cancer Res (2007) 67(16):7850-7855.
72. Ungerechts G, Springfeld C, Frenzke ME, Lampe J, Parker WB, Sorscher EJ, Cattaneo R: An immunocompetent murine model for oncolysis with an armed and targeted measles virus. Mol Ther (2007) 15(11):1991-1997.
73. Eiselein JE, Biggs MW, Walton JR: Treatment of transplanted murine tumors with an oncolytic virus and cyclophosphamide. Cancer Res (1978) 38(11 Pt 1):3817-3822.
74. Purnell DM, Bartlett GL, Kreider JW, Biro TG: Corynebacterium parvum and cyclophosphamide as combination treatment for a murine mammary adenocarcinoma. Cancer Res (1977) 37(4):1137-1140.
75. DiPaolo N, Ni S, Gaggar A, Strauss R, Tuve S, Li ZY, Stone D, Shayakhmetov D, Kiviat N, Touré P, Sow S et al: Evaluation of adenovirus vectors containing serotype 35 fibers for vaccination. Mol Ther (2006) 13(4):756-765.
76. Iankov ID, Blechacz B, Liu C, Schmeckpeper JD, Tarara JE, Federspiel MJ, Caplice N, Russell SJ: Infected cell carriers: A new strategy for systemic delivery of oncolytic measles viruses in cancer virotherapy. Mol Ther (2007) 15(1):114-122.
77. Thorne SH, Negrin RS, Contag CH: Synergistic antitumor effects of immune cell-viral biotherapy. Science (2006) 311(5768):1780- 1784.
78. Mills BA, Roberts RW: Cyclophosphamide-induced cardiomyopathy: A report of two cases and review of the English literature. Cancer (1979) 43(6):2223-2226.
79. Price WE, Keldahl LR: Fatal hemorrhagic cystitis induced by pelvic irradiation and cyclophosphamide therapy. Case reports and review. Minn Med (1990) 73(5):39-41, 44.
80. Zheng M, Deshpande S, Lee S, Ferrara N, Rouse BT: Contribution of vascular endothelial growth factor in the neovascularization process during the pathogenesis of herpetic stromal keratitis. J Virol (2001) 75(20):9828-9835.
81. Zheng M, Schwarz MA, Lee S, Kumaraguru U, Rouse BT: Control of stromal keratitis by inhibition of neovascularization. Am J Pathol (2001) 159(3):1021-1029.
82. Kambara H, Saeki Y, Chiocca EA: Cyclophosphamide allows for in vivo dose reduction of a potent oncolytic virus. Cancer Res (2005) 65(24):11255-11258.
83. Ahmed AR, Hombal SM: Cyclophosphamide (Cytoxan). A review on relevant pharmacology and clinical uses. J Am Acad Dermatol (1984) 11(6):1115-1126.
84. Anderson D, Bishop JB, Garner RC, Ostrosky-Wegman P, Selby PB: Cyclophosphamide: Review of its mutagenicity for an assessment of potential germ cell risks. Mutat Res (1995) 330 (1-2):115-181.
85. Matalon ST, Ornoy A, Lishner M: Review of the potential effects of three commonly used antineoplastic and immunosuppressive drugs (cyclophosphamide, azathioprine, doxorubicin on the embryo and placenta). Reprod Toxicol (2004) 18(2):219-230.
86. Mileshkin L, Prince HM, Rischin D, Zimet A: Severe interstitial pneumonitis following high-dose cyclophosphamide, thiotepa and docetaxel: Two case reports and a review of the literature. Bone Marrow Transplant (2001) 27(5):559-563.
87. Stillwell TJ, Benson RC Jr: Cyclophosphamide-induced hemorrhagic cystitis. A review of 100 patients. Cancer (1988) 61(3):451-457.
88. Zia PK: Cyclophosphamide: A review of its use, and guidelines for administration. Cancer Nurs (1978) 1(1):83-85.