Skip to main content
SpringerLink
Log in

Response as a Measure of Treatment Efficacy in Clinical Trials: Should RECIST Be Abandoned?

  • Chapter
  • First Online:
Controversies in the Management of Gynecological Cancers

  • 1030 Accesses

Abstract

Demonstration of the efficacy and tolerability of new approaches to the treatment of ovarian cancer depends on clinical trials that are well designed with endpoints that are reproducibly and reliably assessable, that reflect clinical benefit, and that lead to the definition of a role, or lack thereof, for that treatment in ovarian cancer. Endpoints for current clinical trials are generally drawn from three options: objective response, progression-free survival, and overall survival. For objective response, current assessments are based on the RECIST criteria. These criteria were the product of an attempt to clarify response criteria and to improve accuracy in the process of measurement. Suggestions that RECIST should be abandoned point to several specific perceived problems: excessive complexity, arbitrariness of definitions for response and progression, lack of usefulness in patients without measurable disease, questions regarding the reliability of RECIST criteria for assessing response particularly in regard to the incorporation of CA-125 as a response criterion, the lack of applicability of RECIST criteria to the assessment of efficacy of many of the new targeted agents, and the difficulty of defining what constitutes clinical benefit. Examination of these criticisms leads to the conclusion that, while there are circumstances in which the RECIST criteria are not applicable to a particular study, the criteria provide useful information in a reliable if somewhat complex way and are no more arbitrary than other endpoints. The clear answer to the question as to whether RECIST should be abandoned is absolutely no. RECIST should be used in those studies for which it is appropriate. On the other hand, efforts to improve further on the RECIST criteria and to go beyond the criteria to incorporate new findings such as molecular markers into endpoints are imperative if studies are to keep pace with the explosion of biologic knowledge.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Thigpen T, duBois A, McAlpine J, DiSaia P, Fujiwara K, Hoskins W, Kristensen G, Mannel R, Markman M, Pfisterer J, Quinn M, Reed N, Swart AM, Berek J, Colombo N, Freyer G, Gallardo D, Plante M, Paveda A, Rubinstein L, Bacon M, Kitchener H, Stuart GC. First-line therapy in ovarian cancer trials. Int J Gynecol Cancer. 2011;21:756–62.

    Article  PubMed  Google Scholar 

  2. Thigpen JT, Vance RB, Khansur T. Second-line chemotherapy for recurrent carcinoma of the ovary. Cancer. 1993;71:1559.

    Article  CAS  PubMed  Google Scholar 

  3. Thigpen T, Blessing J, Homesley H, et al. Cisplatin as salvage therapy in ovarian carcinoma treated initially with single agent paclitaxel: a Gynecologic Oncology Group study (abstract). Proc Am Soc Clin Oncol. 1996;15:286.

    Google Scholar 

  4. Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol. 2001;19:3312–22.

    CAS  PubMed  Google Scholar 

  5. McGuire WP, Blessing JA, Bookman MA, et al. Topotecan has substantial antitumor activity as first-line salvage therapy in platinum-sensitive epithelial ovarian carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2000;18:1062.

    CAS  PubMed  Google Scholar 

  6. Rose PG, Blessing JA, Mayer AR, Homesley HD. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1998;16:405–10.

    CAS  PubMed  Google Scholar 

  7. Markman M, Blessing J, Rubin SC, Connor J, Hanjani P, Waggoner S. Phase II trial of weekly paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a Gynecologic Oncology Group study. Gynecol Oncol. 2006;101:436–40.

    Article  CAS  PubMed  Google Scholar 

  8. Rose PG, Blessing JA, Ball HG, et al. A phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2003;88:130–5.

    Article  CAS  PubMed  Google Scholar 

  9. Miller DS, Blessing JA, Krasner CN, Mannel RJ. A phase II evaluation of pemetrexed (LY231514, IND #40061) in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: a study of the Gynecologic Oncology Group. In: Program and abstracts of the 44th American Society of Clinical Oncology Annual Meeting, Chicago; May 30–June 3 2008. Abstract 5524.

    Google Scholar 

  10. Ferrandina G, Ludovisi M, Lorusso D, et al. Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer. J Clin Oncol. 2008;26:890–6.

    Article  CAS  PubMed  Google Scholar 

  11. Bajetta E, Di Leo A, Biganzoli L, et al. Phase II study of vinorelbine in patients with pretreated advanced ovarian cancer: activity in platinum-resistant disease. J Clin Oncol. 1996;14:2546–51.

    CAS  PubMed  Google Scholar 

  12. Markman M, Hakes T, Reichman B, et al. Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: activity in platinum-resistant disease. J Clin Oncol. 1992;10:243.

    CAS  PubMed  Google Scholar 

  13. Look KY, Muss HB, Blessing JA, Morris M. A phase II trial of 5-fluorouracil and high-dose leucovorin in recurrent epithelial ovarian carcinoma. A Gynecologic Oncology Group Study. Am J Clin Oncol. 1995;18:19.

    Article  CAS  PubMed  Google Scholar 

  14. Vergote I, Micha J, Pippitt Jr C, et al. Phase II study of NKTR-102 in women with platinum resistant/refractory ovarian cancer. Proc ASCO. 2010;28:393s (abstract 5013).

    Google Scholar 

  15. Naumann RW, Symanowski J, Ghamande S, et al. PRECEDENT: a randomized phase II trial comparing EC-145 and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in subjects with platinum-resistant ovarian cancer. Proc ASCO. 2010;28:952s (abstract LBA5012b).

    Google Scholar 

  16. Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007;25:5165–71.

    Article  CAS  PubMed  Google Scholar 

  17. Hatch KD, Beecham JB, Blessing JA, Creasman WT. Responsiveness of patients with advanced ovarian carcinoma to tamoxifen. Cancer. 1991;68:269–71.

    Article  CAS  PubMed  Google Scholar 

  18. Matei D, Sill W, Lankes H, et al. Activity of sorafenib in recurrent ovarian cancer and primary peritoneal carcinomatosis: a Gynecologic Oncology Group trial. J Clin Oncol. 2011;29:69–75.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Kaye SB, Lubinski J, Matulonis U, et al. Phase II, open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADP-Ribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer. J Clin Oncol. 2012;30:372–9.

    Article  CAS  PubMed  Google Scholar 

  20. Matulonis UA, Berlin S, Ivy P, et al. Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. J Clin Oncol. 2009;27:5601–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Buckanovitch R. Activity of cabozantinib in advanced ovarian cancer patients: results from a phase II randomized discontinuation trial. Proc ASCO. 2011;29:334s (abstract 5008).

    Google Scholar 

  22. Manetta A, Tewari K, Podczaski ES. Hexamethylmelamine as a single second-line agent in ovarian cancer: follow-up report and review of the literature. Gynecol Oncol. 1997;66:20.

    Article  CAS  PubMed  Google Scholar 

  23. Thigpen T. A rational approach to the management of recurrent or persistent ovarian carcinoma. Clin Obstet Gynecol. 2012;55: 114–30.

    Article  PubMed  Google Scholar 

  24. Omura G, Blessing JA, Ehrlich CE, et al. A randomized trial of cyclophos-phamide and doxorubicin with or without cisplatin in advanced ovarian carcinoma. A Gynecologic Oncology Group study. Cancer. 1986;57:1725.

    Article  CAS  PubMed  Google Scholar 

  25. Muggia FM, Braly PS, Brady MF, et al. Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2000;18:106.

    CAS  PubMed  Google Scholar 

  26. Burger R, Brady M, Bookman M, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473–83.

    Article  CAS  PubMed  Google Scholar 

  27. Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365:2484–96.

    Article  CAS  PubMed  Google Scholar 

  28. Aghajanian C, Blank SV, Goff BA, et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2010;30:2039–45.

    Article  Google Scholar 

  29. Pujade-Lauraine E. AURELIA: a randomized phase III trial evaluating bevacizumab plus cheothe4rapy for platinum-resistant recurrent ovarian cancer. Proc ASCO. 2012;30:327s.

    Google Scholar 

  30. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst. 2000;92:205–16.

    Article  CAS  PubMed  Google Scholar 

  31. Miller AB, Hoogstraten B, Staquet M, et al. Reporting results of cancer treatment. Cancer. 1981;47:207–14.

    Article  CAS  PubMed  Google Scholar 

  32. Thiesse P, Ollivier L, Di Stefano-Louineau D, Negrier S, Savary J, Pignard K, et al. Response rate accuracy in oncology trials: reasons for interobserver variability. J Clin Oncol. 1997;15:3507–14.

    CAS  PubMed  Google Scholar 

  33. Yoshida S, Miyata Y, Ohtsu A, Boku N, Shirao K, Shimada Y. Significance of and problems in adopting response evaluation criteria in solid tumor RECIST for assessing anti-cancer effects of advanced gastric cancer. Gastric Cancer. 2000;3:128–33.

    Article  PubMed  Google Scholar 

  34. Werner-Wasik M, Xiao Y, Pequignot E, Curran WJ, Hauck W. Assessment of lung cancer response after non-operative therapy: tumor diameter, bidimensional product, and volume. A serial CT scan-based study. Int J Radiat Oncol Biol Phys. 2001;51:56–61.

    Article  CAS  PubMed  Google Scholar 

  35. Kimura M, Tominaga T. Outstanding problems with response evaluation criteria in solid tumors (RECIST) in breast cancer. Breast Cancer. 2002;9:153–9.

    Article  PubMed  Google Scholar 

  36. Trillet-Lenoir V, Freyer G, Kaemmerlen P, Fond A, Pellet O, Lombard-Bohas C, et al. Assessment of tumour response to chemotherapy for metastatic colorectal cancer: accuracy of the RECIST criteria. Br J Radiol. 2002;75:903–8.

    CAS  PubMed  Google Scholar 

  37. Sohaib SA, Turner B, Hanson JA, Farquharson M, Oliver RT, Reznek RH. CT assessment of tumor response to treatment: comparison of linear, cross-sectional and volumetric measures of tumour size. Br J Radiol. 2000;73:1178–84.

    CAS  PubMed  Google Scholar 

  38. Pahani AR, Ollivier L. The RECIST criteria: implications for diagnostic radiologists. Br J Radiol. 2001;74:983–6.

    Google Scholar 

  39. Gehan EA, Tefft MC. Will there be resistance to the RECIST (Response Evaluation Criteria in Solid Tumors)? J Natl Cancer Inst. 2000;92:179–81.

    Article  CAS  PubMed  Google Scholar 

  40. Jaffe C. Measures of response: RECIST, WHO, and new alternatives. J Clin Oncol. 2006;24:3245–51.

    Article  PubMed  Google Scholar 

  41. Michaelis LC, Ratain MJ. Measuring response in a post-RECIST world: from black and white to shades of grey. Nat Rev Cancer. 2006;6:409–14.

    Article  CAS  PubMed  Google Scholar 

  42. Curran SD, Muellner AU, Schwartz LH. Imaging response assessment in oncology. Cancer Imaging. 2006;6:S126–30.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.

    Article  CAS  PubMed  Google Scholar 

  44. Booth CM, Eisenhauer EA. Progression-free survival: meaningful or simply measurable? J Clin Oncol. 2012;30(10):1030–3.

    Article  PubMed  Google Scholar 

  45. Campbell ME, Grothey A, Sargent DJ, Goldberg RM. Waterfall plots provide detailed information on magnitude of response to conventional chemotherapy in advanced colorectal cancer (ACRC) – lessons learned from N9741. J Clin Oncol. 2007;25:4080 (abstract).

    Google Scholar 

  46. Tothill RW, Tinker AV, George J, et al. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clin Cancer Res. 2008;14(16):5198–208.

    Article  CAS  PubMed  Google Scholar 

  47. Anglesio MS, George J, Kulbe H, et al. IL6-STAT3-HIF signaling and therapeutic response to the angiogenesis inhibitor sunitinib in ovarian clear cell cancer. Clin Cancer Res. 2011;17(8):2538–48.

    Article  CAS  PubMed  Google Scholar 

  48. Kurman RJ, Shih IM. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer-shifting the paradigm. Hum Pathol. 2011;42(7):918–31. Review.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Guppy AE, Rustin GJ. CA125 response: can it replace the traditional response criteria in ovarian cancer? Oncologist. 2002;7(5):437–43.

    Article  CAS  PubMed  Google Scholar 

  50. Friedlander M, Butow P, Stockler M, Gainford C, Martyn J, Oza A, Donovan HS, Miller B, King M. Symptom control in patients with recurrent ovarian cancer: measuring the benefit of palliative chemotherapy in women with platinum refractory/resistant ovarian cancer. Int J Gynecol Cancer. 2009;19 Suppl 2:S44–8. Review.

    Article  PubMed  Google Scholar 

  51. Erasmus JJ, Gladish GW, Broemeling L, et al. Interobserver and intraobserver variability in measurement of non-small-cell carcinoma lung lesions: implications for assessment of tumor response. J Clin Oncol. 2003;21:2574–82.

    Article  PubMed  Google Scholar 

  52. Belton AL, Saini S, Liebermann K, et al. Tumour size measurement in an oncology clinical trial: comparison between off-site and on-site measurements. Clin Radiol. 2003;58:311–4.

    Article  CAS  PubMed  Google Scholar 

  53. Husband J, Schwartz L, Spencer J, et al. Evaluation of the response to treatment of solid tumours – a consensus statement of the International Cancer Imaging Society. Br J Cancer. 2004;90:2256–60.

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Geyer CE, Forster J, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355:2733–43.

    Article  CAS  PubMed  Google Scholar 

  55. De Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005.

    Article  PubMed Central  PubMed  Google Scholar 

  56. Rustin GJ, Vergote I, Eisenhauer E, et al. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynaecological Cancer Intergroup (GCIG). Int J Gynecol Cancer. 2011;21(2):419–23.

    Article  PubMed  Google Scholar 

  57. Gronlund B, Hansen HH, Høgdall C, Høgdall EV, Engelholm SA. Do CA125 response criteria overestimate tumour response in second-line treatment of epithelial ovarian carcinoma? Br J Cancer. 2004;90(2):377–82.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Gronlund B, Høgdall C, Hilden J, Engelholm SA, Høgdall EV, Hansen HH. Should CA-125 response criteria be preferred to response evaluation criteria in solid tumors (RECIST) for prognostication during second-line chemotherapy of ovarian carcinoma? J Clin Oncol. 2004;22(20):4051–8.

    Article  PubMed  Google Scholar 

  59. Coleman RL, Gordon A, Barter J, et al. Early changes in CA125 after treatment with pegylated liposomal doxorubicin or topotecan do not always reflect best response in recurrent ovarian cancer patients. Oncologist. 2007;12:72–8.

    Article  CAS  PubMed  Google Scholar 

  60. Choi H. Critical issues in response evaluation on computed tomography: lessons from the gastrointestinal stromal tumor model. Curr Oncol Rep. 2005;7:307–11.

    Article  PubMed  Google Scholar 

  61. van der Veldt AA, Meijer ink MR, van den Eertwegh AJ, Haanen JB, Boven E. Choi response criteria for early prediction of clinical outcome in patients with metastatic renal cell cancer treated with sunitinib. Br J Cancer. 2010;102(5):803–9.

    Article  PubMed Central  PubMed  Google Scholar 

  62. Ratain MJ, Eckhardt SJ. Phase II studies of modern drugs directed against new targets: if you are fazed, too, then resist RECIST. J Clin Oncol. 2004;22:4442–5.

    Article  PubMed  Google Scholar 

  63. Escudier B, Eisen T. Stadler WM Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356(2):125–34.

    Article  CAS  PubMed  Google Scholar 

  64. Bronchud MH, Howell A, Crowther D, et al. The use of granulocyte colony-stimulating factor to increase the intensity of treatment with doxorubicin in patients with advanced breast and ovarian cancer. Br J Cancer. 1989;60:121–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Larson SM, Schwartz LH. 18F-FDG PET as a candidate for qualified biomarker: functional assessment of treatment response in oncology. J Nucl Med. 2006;47:901–3.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology, The Prince of Wales Hospital, Barker Street, Randwick, Sydney, NSW, 2031, Australia

    Michael Friedlander PhD, FRACP

  2. Medicine: Oncology-Hematology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA

    James Tate Thigpen MD

Authors
  1. Michael Friedlander PhD, FRACP
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James Tate Thigpen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Friedlander PhD, FRACP .

Editor information

Editors and Affiliations

  1. UCL Cancer Institute, University College London, London, United Kingdom

    Jonathan A. Ledermann

  2. Radiation Oncology, Leiden University Medical Center, Leiden, The Netherlands

    Carien L. Creutzberg

  3. Royal Women’s Hospital, The University of Melbourne, Melbourne, Australia

    Michael A. Quinn

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag London

About this chapter

Cite this chapter

Friedlander, M., Thigpen, J.T. (2014). Response as a Measure of Treatment Efficacy in Clinical Trials: Should RECIST Be Abandoned?. In: Ledermann, J., Creutzberg, C., Quinn, M. (eds) Controversies in the Management of Gynecological Cancers. Springer, London. https://doi.org/10.1007/978-0-85729-910-9_9

Download citation

  • DOI: https://doi.org/10.1007/978-0-85729-910-9_9

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-0-85729-909-3

  • Online ISBN: 978-0-85729-910-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation