• Please log in or register to access this feature.

Original Article

You have full text access to this OnlineOpen article

A Phase I trial of pulse calcitriol in patients with refractory malignancies

Pulse dosing permits substantial dose escalation

  1. Tomasz M. Beer M.D.1,†,*,
  2. Myrna Munar Pharm. D.2,
  3. W. David Henner M.D., Ph.D.1

Article first published online: 13 JUN 2001

DOI: 10.1002/1097-0142(20010615)91:12<2431::AID-CNCR1278>3.0.CO;2-3

Issue

Cancer

Cancer

Volume 91, Issue 12, pages 2431–2439, 15 June 2001

Additional Information

How to Cite

Beer, T. M., Munar, M. and Henner, W. D. (2001), A Phase I trial of pulse calcitriol in patients with refractory malignancies. Cancer, 91: 2431–2439. doi: 10.1002/1097-0142(20010615)91:12<2431::AID-CNCR1278>3.0.CO;2-3

Author Information

  1. 1

    Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland, Oregon

  2. 2

    Oregon State University College of Pharmacy at Oregon Health Sciences University, Portland, Oregon

  1. †

    Fax: (503) 494-6197

*Division of Hematology and Medical Oncology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd., Mail Code L-586, Portland, OR 97201

  1. †

    Fax: (503) 494-6197

Publication History

  1. Issue published online: 13 JUN 2001
  2. Article first published online: 13 JUN 2001
  3. Manuscript Revised: 12 MAR 2001
  4. Manuscript Accepted: 12 MAR 2001
  5. Manuscript Received: 5 OCT 2000

Funded by

  • PHS. Grant Number: 5 M01 RR00334

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (112K)

REFERENCES

  • 1
    Holick MF. Noncalcemic actions of 1,25-dihydroxyvitamin D3 and clinical applications. Bone 1995; 17(2 Suppl ): 107S–111S.
  • 2
    Peehl DM, Skowronski RJ, Leung GK, Wong ST, Stamey TA, Feldman D. Antiproliferative effects of 1,25-dihydroxyvitamin D3 on primary cultures of human prostatic cells. Cancer Res 1994; 54(3): 805–10.
  • 3
    Skowronski RJ, Peehl DM, Feldman D. Vitamin D and prostate cancer: 1,25 dihydroxyvitamin D3 receptors and actions in human prostate cancer cell lines. Endocrinology 1993; 132(5): 1952–60.
  • 4
    Schwartz GG, Oeler TA, Uskokovic MR, Bahnson RR. Human prostate cancer cells: inhibition of proliferation by vitamin D analogs. Anticancer Res 1994; 14(3A): 1077–81.
  • 5
    Colston KW, Chander SK, Mackay AG, Coombes RC. Effects of synthetic vitamin D analogues on breast cancer cell proliferation in vivo and in vitro. Biochem Pharmacol 1992; 44(4): 693–702.
  • 6
    Higashimoto Y, Ohata M, Nishio K, Iwamoto YV, Fujimoto H, Uetani K, et al. 1 alpha, 25-dihydroxyvitamin D3 and all-trans-retinoic acid inhibit the growth of a lung cancer cell line. Anticancer Res 1996; 16(5A): 2653–9.
  • 7
    Cross HS, Huber C, Peterlik M. Antiproliferative effect of 1,25-dihydroxyvitamin D3 and its analogs on human colon adenocarcinoma cells (CaCo-2): influence of extracellular calcium. Biochem Biophys Res Commun 1991; 179(1): 57–62.
  • 8
    Zugmaier G, Jager R, Grage B, Gottardis MM, Havemann K, Knabbe C. Growth-inhibitory effects of vitamin D analogues and retinoids on human pancreatic cancer cells. Br J Cancer 1996; 73(11): 1341–6.
  • 9
    Yabushita H, Hirata M, Noguchi M, Nakanishi M. Vitamin D receptor in endometrial carcinoma and the differentiation-inducing effect of 1,25-dihydroxyvitamin D3 on endometrial carcinoma cell lines. J Obstet Gynaecol Res 1996; 22(6): 529–39.
  • 10
    Abe E, Miyaura C, Sakagami H, Takeda M, Konno K, Yamazaki T, et al. Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A 1981; 78(8): 4990–4.
  • 11
    Colston K, Colston MJ, Feldman D. 1,25-dihydroxyvitamin D3 and malignant melanoma: the presence of receptors and inhibition of cell growth in culture. Endocrinology 1981; 108(3): 1083–6.
  • 12
    Shabahang M, Buffan AE, Nolla JM, Schumaker LM, Brenner RV, Buras RR, et al. The effect of 1, 25-dihydroxyvitamin D3 on the growth of soft-tissue sarcoma cells as mediated by the vitamin D receptor. Ann Surg Oncol 1996; 3(2): 144–9.
  • 13
    Tokuumi Y. [Correlation between the concentration of 1,25 alpha dihydroxyvitamin D3 receptors and growth inhibition, and differentiation of human osteosarcoma cells induced by vitamin D3]. Nippon Seikeigeka Gakkai Zasshi 1995; 69(4): 181–90.
  • 14
    Eisman JA, Barkla DH, Tutton PJ. Suppression of in vivo growth of human cancer solid tumor xenografts by 1,25-dihydroxyvitamin D3. Cancer Res 1987; 47(1): 21–5.
  • 15
    McElwain MC, Dettelbach MA, Modzelewski RA, et al. Antiproliferative effects in vitro and in vivo of 1,25-dihydroxyvitamin D3 analog in a squamous cell carcinoma model system. Mol Cell Diff 1995; 3(1): 31–50.
  • 16
    Cohen SM, Saulenas AM, Sullivan CR, Albert DM. Further studies of the effect of vitamin D on retinoblastoma. Inhibition with 1,25-dihydroxycholecalciferol. Arch Ophthalmol 1988;106(4): 541–3.
  • 17
    Campbell MJ, Koeffler HP. Toward therapeutic intervention of cancer by vitamin D compounds. J Natl Cancer Inst 1997; 89(3): 182–5.
  • 18
    Liu M, Lee MH, Cohen M, Bommakanti M, Freedman LP. Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev 1996; 10(2): 142–53.
  • 19
    Hengst L, Reed SI. Translational control of p27Kip1 accumulation during the cell cycle. Science 1996; 271(5257): 1861–4.
  • 20
    Kobayashi T, Hashimoto K, Yoshikawa K. Growth inhibition of human keratinocytes by 1,25-dihydroxyvitamin D3 is linked to dephosphorylation of retinoblastoma gene product. Biochem Biophys Res Commun 1993; 196(1): 487–93.
  • 21
    James SY, Mackay AG, Colston KW. Effects of 1,25 dihydroxyvitamin D3 and its analogues on induction of apoptosis in breast cancer cells. J Steroid Biochem Mol Biol 1996; 58(4): 395–401.
  • 22
    Tang W, Ziboh VA, Isseroff RR, Martinez D. Novel regulatory actions of 1 alpha,25-dihydroxyvitamin D3 on the metabolism of polyphosphoinositides in murine epidermal keratinocytes. J Cell Physiol 1987; 132(1): 131–6.
    Direct Link:
  • 23
    Haugen JD, Pittelkow MR, Zinsmeister AR, Kumar R. 1 alpha,25-dihydroxyvitamin D3 inhibits normal human keratinocyte growth by increasing transforming growth factor beta 2 release. Biochem Biophys Res Commun 1996; 229(2): 618–23.
  • 24
    Kim HJ, Abdelkader N, Katz M, McLane JA. 1,25-Dihydroxy-vitamin-D3 enhances antiproliferative effect and transcription of TGF-beta1 on human keratinocytes in culture. J Cell Physiol 1992; 151(3): 579–87.
    Direct Link:
  • 25
    Vink-van Wijngaarden T, Pols HA, Buurman CJ, Birkenhager JC, van Leeuwen JP. Inhibition of insulin- and insulin-like growth factor-I-stimulated growth of human breast cancer cells by 1,25-dihydroxyvitamin D3 and the vitamin D3 analogue EB1089. Eur J Cancer 1996; 32A(5): 842–8.
  • 26
    Drivdahl RH, Loop SM, Andress DL, Ostenson RC. IGF-binding proteins in human prostate tumor cells: expression and regulation by 1,25-dihydroxyvitamin D3. Prostate 1995; 26(2): 72–9.
    Direct Link:
  • 27
    Schwartz GG, Wang MH, Zang M, Singh RK, Siegal GP. 1 alpha,25-Dihydroxyvitamin D (calcitriol) inhibits the invasiveness of human prostate cancer cells. Cancer Epidemiol Biomarkers Prev 1997; 6(9): 727–32.
  • 28
    Majewski S, Szmurlo A, Marczak M, Jablonska S, Bollag W. Inhibition of tumor cell-induced angiogenesis by retinoids, 1,25-dihydroxyvitamin D3 and their combination. Cancer Lett 1993; 75(1): 35–9.
  • 29
    Osborn JL, Schwartz GG, Smith DC, Bahnson R, Day R, Trump DL. Phase II trial of oral 1,25-dihydroxyvitamin D (Calcitriol) in hormone refractory prostate cancer. Urol Oncol 1995; 1: 195–198.
  • 30
    Koeffler HP, Hirji K, Itri L. 1,25-Dihydroxyvitamin D3: in vivo and in vitro effects on human preleukemic and leukemic cells. Cancer Treat Rep 1985; 69(12): 1399–407.
  • 31
    Rustin GJ, Quinnell TG, Johnson J, Clarke H, Nelstrop AE, Bollag W. Trial of isotretinoin and calcitriol monitored by CA 125 in patients with ovarian cancer. Br J Cancer 1996; 74(9): 1479–81.
  • 32
    Gross C, Stamey T, Hancock S, Feldman D. Treatment of early recurrent prostate cancer with 1,25-dihydroxyvitamin D3 (calcitriol). J Urol 1998; 159(6): 2035–9; discussion 2039–40.
  • 33
    Smith DC, Johnson CS, Freeman CC, Muindi J, Wilson JW, Trump DL. A Phase I trial of calcitriol (1,25-dihydroxycholecalciferol) in patients with advanced malignancy. Clin Cancer Res 1999; 5(6): 1339–45.
  • 34
    Skowronski RJ, Peehl DM, Feldman D. Actions of vitamin D3, analogs on human prostate cancer cell lines: comparison with 1,25-dihydroxyvitamin D3. Endocrinology 1995; 136(1): 20–6.
  • 35
    Light BW, Yu WD, McElwain MC, Russell DM, Trump DL, Johnson CS. Potentiation of cisplatin antitumor activity using a vitamin D analogue in a murine squamous cell carcinoma model system. Cancer Res 1997; 57(17): 3759–64.
  • 36
    Hershberger PA, Modzelewski RA, Trump DL, Johnson CS. Calcitriol inhibits p21waf1cip1 (p21) expression and sensitizes SCC cells to cisplatin cytotoxicity in vitro and in vivo. Proc AACR 1999; 40: 12.
  • 37
    Johnson CS, Yu WD, Hershberger PA, Modzelewski RA, Trump DL. 1,25-dihydroxycholecalciferol (1,25D3) and paclitaxel: a new therapeutic combination in prostate tumor model systems. In: NameII, editor. Proceedings of ASCO; 1998 Mmm dd–dd; city of conference. City where published: American Society of Clinical Oncology, 1998: 17: 215a.
  • 38
    Papapoulos SE, Clemens TL, Sandler LM, Fraher LJ, Winer J, O'Riordan JL. The effect of renal function on changes in circulating concentrations of 1,25-dihydroxycholecalciferol after an oral dose. Clin Sci 1982; 62(4): 427–9.
  • 39
    Mason RS, Lissner D, Posen S, Norman AW. Blood concentrations of dihydroxylated vitamin D metabolites after an oral dose. Br Med J 1980; 280(6212): 449–50.
  • 40
    Geusens P, Vanderschueren D, Verstraeten A, Dequeker J, Devos P, Bouillon R. Short-term course of 1,25(OH)2D3 stimulates osteoblasts but not osteoclasts in osteoporosis and osteoarthritis. Calcif Tissue Int 1991; 49(3): 168–73.
  • 41
    Nelson M. The validation of dietary assessment. In: MergetsBM, NelsonM, editors. Design concepts in nutritional epidemiology. Oxford: Oxford University Press, 1997: 241–72.
  • 42
    Gordon NH, Willson JK. Using toxicity grades in the design and analysis of cancer phase I clinical trials. Stat Med 1992; 11(16): 2063–75.
    Direct Link:
  • 43
    Storer BE. Design and analysis of phase I clinical trials. Biometrics 1989; 45(3): 925–37.
  • 44
    Reinhardt TA, Horst RL, Orf JW, Hollis BW. A microassay for 1,25-dihydroxyvitamin D not requiring high performance liquid chromatography: application to clinical studies. J Clin Endocrinol Metab 1984; 58(1): 91–8.
  • 45
    GibaldiM, editor. Estimation of area under the curve biopharmaceutics and clinical pharmacokinetics. 3rd ed. Philadelphia: Lea & Febiger, 1984; 315–6.
  • 46
    [Anonymous]. Consensus development conference statement. J Bone Miner Res 1991; 6 Suppl 2: S9–13.
View Full Article (HTML) Get PDF (112K)