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Phase II study of CT-2103 as first- or second-line chemotherapy in patients with metastatic breast cancer: unexpected incidence of hypersensitivity reactions

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Summary

This study evaluated the safety and efficacy of CT-2103, a novel conjugate of paclitaxel and poly-l-glutamate, in patients with HER2-negative, metastatic breast cancer who had received 0 or 1 prior lines of chemotherapy. Although CT-2103 had activity in this small study, neurotoxicity and hypersensitivity reactions were more frequent in this patient population than expected, and led to early termination of the trial. Purpose To evaluate the safety and efficacy of CT-2103, a novel conjugate of paclitaxel and poly-l-glutamate, in patients with metastatic breast cancer who had received 0 or 1 prior lines of chemotherapy. Patients and Methods Eighteen women with HER2-negative breast cancer were enrolled. Patients received intravenous CT-2103 at a dose of 175 mg/m2 of conjugated paclitaxel over 10 min every 3 weeks, without routine premedication. Eighty-three percent of women had received prior chemotherapy as part of adjuvant (39%), metastatic (17%), or both adjuvant and metastatic (28%) treatment. Three patients (17%) had previously received a taxane in the adjuvant setting. Results Objective responses were observed in 4 of 18 patients (overall response rate, 22%, 95% confidence interval, 6 to 48%). Grade 3 or 4 neuropathy was observed in four patients. Grade 3 or 4 hypersensitivity reactions (HSR) were observed in four patients; none occurred prior to cycle 4 of therapy. Because of the higher-than-expected rate of HSR, the study was terminated early. Conclusion Although CT-2103 had activity in this small study of women with HER2-negative metastatic breast cancer, neurotoxicity and hypersensitivity reactions were more frequent in this patient population than expected. Hypersensitivity reactions were most likely to occur in later cycles of treatment, suggesting a true drug allergy, distinct from the HSR typically seen with standard paclitaxel.

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References

  1. Paridaens R, Biganzoli L, Bruning P, Klijn JG, Gamucci T, Houston S, Coleman R, Schachter J, Van Vreckem A, Sylvester R, Awada A, Wildiers J, Piccart M (2000) Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer Randomized Study with cross-over. J Clin Oncol 18(4):724–733

    PubMed  CAS  Google Scholar 

  2. Seidman AD, Tiersten A, Hudis C, Gollub M, Barrett S, Yao TJ, Lepore J, Gilewski T, Currie V, Crown J et al (1995) Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. J Clin Oncol 13(10):2575–2581

    PubMed  CAS  Google Scholar 

  3. Nabholtz JM, Gelmon K, Bontenbal M, Spielmann M, Catimel G, Conte P, Klaassen U, Namer M, Bonneterre J, Fumoleau P, Winograd B (1996) Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer. J Clin Oncol 14(6):1858–1867

    PubMed  CAS  Google Scholar 

  4. Chevallier B, Fumoleau P, Kerbrat P, Dieras V, Roche H, Krakowski I, Azli N, Bayssas M, Lentz MA, Van Glabbeke M (1995) Docetaxel is a major cytotoxic drug for the treatment of advanced breast cancer: a phase II trial of the clinical screening cooperative group of the European organization for research and treatment of cancer. J Clin Oncol 13(2):314–322

    PubMed  CAS  Google Scholar 

  5. Burstein HJ, Manola J, Younger J, Parker LM, Bunnell CA, Scheib R, Matulonis UA, Garber JE, Clarke KD, Shulman LN, Winer EP (2000) Docetaxel administered on a weekly basis for metastatic breast cancer. J Clin Oncol 18(6):1212–1219

    PubMed  CAS  Google Scholar 

  6. Chan S, Friedrichs K, Noel D, Pinter T, Van Belle S, Vorobiof D, Duarte R, Gil Gil M, Bodrogi I, Murray E, Yelle L, von Minckwitz G, Korec S, Simmonds P, Buzzi F, Gonzalez Mancha R, Richardson G, Walpole E, Ronzoni M, Murawsky M, Alakl M, Riva A, Crown J (1999) Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol 17(8):2341–2354

    PubMed  CAS  Google Scholar 

  7. Ibrahim NK, Samuels B, Page R, Doval D, Patel KM, Rao SC, Nair MK, Bhar P, Desai N, Hortobagyi GN (2005) Multicenter phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer. J Clin Oncol 23(25):6019–6026

    Article  PubMed  CAS  Google Scholar 

  8. Winer EP, Berry DA, Woolf S, Duggan D, Kornblith A, Harris LN, Michaelson RA, Kirshner JA, Fleming GF, Perry MC, Graham ML, Sharp SA, Keresztes R, Henderson IC, Hudis C, Muss H, Norton L (2004) Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: cancer and leukemia group B trial 9342. J Clin Oncol 22(11):2061–2068

    Article  PubMed  CAS  Google Scholar 

  9. O’Shaughnessy J, Tjulandin S, Davidson N, Shaw H, Desai N, Hawkins M, Gradishar WJ (2003) ABI-007 (Abraxane), a nanoparticle albumin-bound (NAB) paclitaxel demonstrates superior efficacy vs. Taxol in MBC: a phase III trial. In: San Antonio breast cancer symposium

  10. Seidman AD, Berry D, Cirrincione C, Harris L, Dressler L, Muss H, Naughton M, Norton L, Winer E, Hudis C (2004) CALGB 9840: phase III study of weekly (W) paclitaxel (P) via 1-hour (h) infusion versus standard (S) 3 h infusion every third week in the treatment of metastatic breast cancer (MBC), with trastuzumab (T) for HER2 positive MBC and randomized for T in HER2 normal MBC. J Clin Oncol 22(14S): abstract 512

    Google Scholar 

  11. Sledge GW, Neuberg D, Bernardo P, Ingle JN, Martino S, Rowinsky EK, Wood WC (2003) Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol 21(4):588–592

    Article  PubMed  Google Scholar 

  12. Jones SE, Erban J, Overmoyer B, Budd GT, Hutchins L, Lower E, Laufman L, Sundaram S, Urba WJ, Pritchard KI, Mennel R, Richards D, Olsen S, Meyers ML, Ravdin PM (2005) Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol 23(24):5542–5551

    Article  PubMed  CAS  Google Scholar 

  13. Wiernik PH, Schwartz EL, Strauman JJ, Dutcher JP, Lipton RB, Paietta E (1987) Phase I clinical and pharmacokinetic study of taxol. Cancer Res 47(9):2486–2493

    PubMed  CAS  Google Scholar 

  14. Kris MG, O’Connell JP, Gralla RJ, Wertheim MS, Parente RM, Schiff PB, Young CW (1986) Phase I trial of taxol given as a 3-hour infusion every 21 days. Cancer Treat Rep 70(5):605–607

    PubMed  CAS  Google Scholar 

  15. Grem JL, Tutsch KD, Simon KJ, Alberti DB, Willson JK, Tormey DC, Swaminathan S, Trump DL (1987) Phase I study of taxol administered as a short i.v. infusion daily for 5 days. Cancer Treat Rep 71(12):1179–1184

    PubMed  CAS  Google Scholar 

  16. Robson L, Verrill M, Lind M, Simmons P, Perren T, Coombes C, Earl H, Calvert H, Campbell M, Bolton M (2003) A phase 2 study of CT-2103, a poly(L-glutamic acid)-paclitaxel conjugate administered every 3 weeks in patients with advanced breast cancer. Proc Am Soc Clin Oncol 22:42

    Google Scholar 

  17. Miller KD, Wang M, Gralow J, Dickler M, Cobleigh MA, Perez EA, Shenkier TN, Davidson NE (2005) A randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer. In: American Society of Clinical Oncology 41st annual meeting

  18. Bonomi P, Paz-Ares L, Langer C (2005) Xyotax vs docetaxel for the second line treatment of non-small cell lung cancer (NSCLC): the STELLAR 2 phase III trial. Lung Cancer 29(Suppl 2):S35

    Article  Google Scholar 

  19. Langer CJ, Socinski MA, Ross H, O’Byrne KJ (2005) Paclitaxel poliglumex (PPX)/carboplatin vs paclitaxel/carboplatin for PS2 patients with chemotherapy-naive advanced non-small cell lung cancer: a phase III study. J Clin Oncol 23(16S):623s

    Google Scholar 

  20. Sabbatini P, Aghajanian C, Dizon D, Anderson S, Dupont J, Brown JV, Peters WA, Jacobs A, Mehdi A, Rivkin S, Eisenfeld AJ, Spriggs D (2004) Phase II study of CT-2103 in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. J Clin Oncol 22(22):4523–4531

    Article  PubMed  CAS  Google Scholar 

  21. Markman M, Kennedy A, Webster K, Elson P, Peterson G, Kulp B, Belinson J (1999) Clinical features of hypersensitivity reactions to carboplatin. J Clin Oncol 17(4):1141

    PubMed  CAS  Google Scholar 

  22. Schiavetti A, Varrasso G, Maurizi P, Castello MA (1999) Hypersensitivity to carboplatin in children. Med Pediatr Oncol 32(3):183–185

    Article  PubMed  CAS  Google Scholar 

  23. Polyzos A, Tsavaris N, Kosmas C, Arnaouti T, Kalahanis N, Tsigris C, Giannopoulos A, Karatzas G, Giannikos L, Sfikakis PP (2001) Hypersensitivity reactions to carboplatin administration are common but not always severe: a 10-year experience. Oncology 61(2):129–133

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

Supported by Cell Therapeutics Inc., Seattle, WA.

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Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA, 02115, USA

    Nancy U. Lin, Leroy M. Parker, Harold J. Burstein, Margaret Haldoupis, Nicole Ryabin, Eric P. Winer & Lawrence N. Shulman

  2. Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Steven E. Come

  3. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA

    Rebecca Gelman

Authors
  1. Nancy U. Lin
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  2. Leroy M. Parker
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  3. Steven E. Come
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  4. Harold J. Burstein
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  5. Margaret Haldoupis
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  6. Nicole Ryabin
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  7. Rebecca Gelman
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  8. Eric P. Winer
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  9. Lawrence N. Shulman
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Correspondence to Lawrence N. Shulman.

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Lin, N.U., Parker, L.M., Come, S.E. et al. Phase II study of CT-2103 as first- or second-line chemotherapy in patients with metastatic breast cancer: unexpected incidence of hypersensitivity reactions. Invest New Drugs 25, 369–375 (2007). https://doi.org/10.1007/s10637-007-9034-y

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  • DOI: https://doi.org/10.1007/s10637-007-9034-y

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