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Chemotherapy for Cervical Cancer

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Uterine Cervical Cancer

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Abstract

Chemotherapy has a potential role in all stages of cervical cancer. Chemotherapy can be administered in the neoadjuvant, concurrent with radiation, adjuvant and palliative setting. Randomised evidence has clearly established the role of chemotherapy for uterine cervical cancer in the concurrent with radiation and metastatic/palliative settings.

The exact role of neoadjuvant chemotherapy preoperatively in early stage disease or pre-chemo-radiation in locally advanced disease has not yet been proven and is currently under investigation in the EORTC 55994 and INTERLACE trial, respectively. Neoadjuvant chemotherapy is also appealing to reduce tumour bulk and enable fertility-sparing surgical management and warrants further investigation. During radiation for locally advanced cervical cancer, the addition of chemotherapy significantly improves survival and is therefore an established standard of care. Weekly cisplatin chemotherapy is the most commonly used regimen, but a variety of regimens are used worldwide. Adjuvant chemotherapy after chemo-radiation in theory could improve survival but is unproven and is therefore being investigated within the OUTBACK study. In the metastatic or inoperable recurrent setting, the majority of patients will be managed with combination chemotherapy, e.g. carboplatin or cisplatin with paclitaxel, if fitness allows. The addition of bevacizumab to this combination significantly improves survival and is approved in many countries as first-line treatment if patients are fit enough. Second-line treatment is less evidence-based with commonly used regimens including single-agent carboplatin, single-agent paclitaxel often administered weekly, topotecan and others. In general, if patients are fit at the time of needing second-line treatment, referral to specialist trial units for phase I/II trial is recommended.

Neuroendocrine (i.e. small-cell) tumours are a rare histological subtype of uterine cervical cancer accounting for approximately 2% of all cervical cancer diagnoses. This subtype is more chemosensitive, and management is therefore similar to that for small-cell lung cancer. The use of cisplatin and etoposide chemotherapy is therefore critical in the management of all stages of disease. This chapter discusses the evidence available and current trials in all of these settings to clarify the important role of chemotherapy in uterine cervical cancer.

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References

  1. Abdel-Wahab M, et al. Global access to radiotherapy in low- and middle-income countries. Clin Oncol (R Coll Radiol). 2017;29(2):99–104.

    Article  CAS  Google Scholar 

  2. Clere N, et al. The human papillomavirus type 18 E6 oncoprotein induces vascular endothelial growth factor 121 (VEGF121) transcription from the promoter through a p53-independent mechanism. Exp Cell Res. 2007;313:3239–50.

    Article  CAS  PubMed  Google Scholar 

  3. Comparetto C, et al. Cervical cancer screening: a never-ending developing program. World J Clin Cases. 2015;3(7):614–24.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Colombo N, et al. Cervical cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up ESMO Guidelines Working Group. Ann Oncol. 2012;23(Suppl 7):vii27–32.

    PubMed  Google Scholar 

  5. Landoni F, et al. Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet. 1997;350(9077):535–40.

    Article  CAS  PubMed  Google Scholar 

  6. Perez CA, et al. Radiation therapy alone in the treatment of carcinoma of uterine cervix. I. Analysis of tumor recurrence. Cancer. 1983;51(8):1393–402.

    Article  CAS  PubMed  Google Scholar 

  7. Jampolis S, et al. Analysis of sites and causes of failures of irradiation in invasive squamous cell carcinoma of the intact uterine cervix. Radiology. 1975;115:681–5.

    Article  CAS  PubMed  Google Scholar 

  8. Rogers L, et al. Radiotherapy and chemoradiation after surgery for early cervical cancer. Cochrane Database Syst Rev. 2012;5:CD007583. https://doi.org/10.1002/14651858.CD007583.pub3.

    Article  Google Scholar 

  9. O’Quinn AG, et al. Guidelines for conservative hysterectomy after irradiation. Gynecol Oncol. 1980;9:68–79.

    Article  PubMed  Google Scholar 

  10. Seiwet TY, et al. The concurrent chemoradiation paradigm – general principles. Nat Clin Pract Oncol. 2007;4(2):86–100.

    Article  Google Scholar 

  11. Wilson GD, et al. Biologic basis for combining drugs with radiation. Semin Radiat Oncol. 2006;16:2–9.

    Article  PubMed  Google Scholar 

  12. Yang LX, et al. Irradiation enhances cellular uptake of carboplatin. Int J Radiat Oncol Biol Phys. 1995;33(3):641–6.

    Article  CAS  PubMed  Google Scholar 

  13. Morris M, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. New Engl J Med. 1991;340(15):1137–43.

    Article  Google Scholar 

  14. Keys HM, et al. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999;340(15):1154–61.

    Article  CAS  PubMed  Google Scholar 

  15. Peters WA, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncology. 2000;18(8):1606–13.

    Article  CAS  Google Scholar 

  16. Rose PG, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. New Engl J Med. 1999;340(15):1144–53.

    Article  CAS  PubMed  Google Scholar 

  17. Whitney CW, et al. Randomised comparison of fluorouracil plus cisplatin versus hydroxyurea in stage IIB/IVA in carcinoma of the cervix. J Clin Oncol. 1999;17:1339–48.

    Article  CAS  PubMed  Google Scholar 

  18. McCormack M, et al. A national audit of chemo-radiation practice for cervical carcinoma in the United Kingdom. Royal College of Radiologists Annual Scientific Meeting 2001. Clin Oncol. 2001;13:318–9.

    Google Scholar 

  19. CCCMAC. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol. 2008;26:5802–12.

    Article  Google Scholar 

  20. Dueñas-González A, et al. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011;29:1678.

    Article  PubMed  Google Scholar 

  21. Fyles AW, et al. Prognostic factors in patients with cervix cancer treated by radiation therapy: results of a multiple regression analysis. Radiother Oncol. 1995;35:107–17.

    Article  CAS  PubMed  Google Scholar 

  22. Perez CA, et al. Carcinoma of the uterine cervix: I. Impact of prolongation of overall treatment time and timing of brachytherapy on outcome of radiation therapy. Int J Radiat Oncol Biol Phys. 1995;32:1275–88.

    Article  CAS  PubMed  Google Scholar 

  23. Zarba JJ, et al. A phase I–II study of weekly cisplatin and gemcitabine with concurrent radiotherapy in locally advanced cervical cancer. Ann Oncol. 2003;14:1285–90.

    Article  CAS  PubMed  Google Scholar 

  24. Umanzor J, et al. Concurrent cisplatin/gemcitabine along with radiotherapy in locally advanced cervical carcinoma: a phase II trial. Gynecol Oncol. 2006;100:70–5.

    Article  CAS  PubMed  Google Scholar 

  25. Rose PG, et al. A phase I study of gemcitabine followed by cisplatin concurrent with whole pelvic radiation therapy in locally advanced cervical cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2007;107:274–9.

    Article  CAS  PubMed  Google Scholar 

  26. Puget Sound Oncology Consortium. Weekly gemcitabine and cisplatin in combination with pelvic radiation in the primary therapy of cervical cancer: a phase I trial of the Puget Sound Oncology Consortium. Gynecol Oncol. 2006;101:429–35.

    Article  Google Scholar 

  27. Kim YS, et al. Prospective randomized comparison of monthly fluorouracil and cisplatin versus weekly cisplatin concurrent with pelvic radiotherapy and high-dose rate brachytherapy for locally advanced cervical cancer. Gynecol Oncol. 2008;108:195.

    Article  CAS  PubMed  Google Scholar 

  28. Pfaendler KS, et al. Changing paradigms in the systemic treatment of advanced cervical cancer. Am J Obstet Gynecol. 2016;214(1):22–30.

    Article  PubMed  Google Scholar 

  29. Barter JF, et al. Diagnosis and treatment of pulmonary metastases from cervical carcinoma. Gynecol Oncol. 1990;38(3):347–51.

    Article  CAS  PubMed  Google Scholar 

  30. Zola P, et al. Could follow-up different modalities play a role in asymptomatic cervical cancer relapses diagnosis? An Italian multicenter retrospective analysis. Gynecol Oncol. 2007;107(Suppl. 1 (1)):S150–4.

    Article  CAS  PubMed  Google Scholar 

  31. Carlson V, et al. Distant metastases in squamous cell carcinoma of the uterine cervix. Radiology. 1967;88(5):961–6.

    Article  CAS  PubMed  Google Scholar 

  32. Friedlander M, Grogan M, U.S. Preventative Services Task Force. Guidelines for the treatment of recurrent and metastatic cervical cancer. Oncologist. 2002;7(4):342–7.

    PubMed  Google Scholar 

  33. Thigpen T, et al. Cis-dichlorodiammine platinum (II) in the treatment of gynecologic malignancies: phase II trials by the Gynecologic Oncology Group. Cancer Treat Rep. 1979;63(9–10):1549–55.

    CAS  PubMed  Google Scholar 

  34. Ishikawa H, et al. Platelet-sparing effect of paclitaxel in heavily pretreated ovarian cancer patients. Int J Clin Oncol. 2002;7(5):330–3.

    CAS  PubMed  Google Scholar 

  35. Kitagawa R, et al. Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical cancer: the open-label randomized phase III trial JCOG0505. J Clin Oncol. 2015;33(19):2129–35.

    Article  CAS  PubMed  Google Scholar 

  36. Lorusso D, et al. A systematic review comparing cisplatin and carboplatin plus paclitaxel-based chemotherapy for recurrent or metastatic cervical cancer. Gynecol Oncol. 2014;133(1):117–23.

    Article  CAS  PubMed  Google Scholar 

  37. Moore DH, et al. Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a Gynaecologic Oncology Group study. J Clin Oncol. 2004;22(15):3113–9.

    Article  CAS  PubMed  Google Scholar 

  38. Monk BJ, et al. Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2009;27(28):4649–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. McKim A, et al. An economic analysis of cisplatin alone versus cisplatin doublets in the treatment of women with advanced or recurrent cervical cancer. Eur J Gynaecol Oncol. 2016;37(3):353–6.

    CAS  PubMed  Google Scholar 

  40. Moore DH, et al. Prognostic factors for response to cisplatin-based chemotherapy in advanced cervical carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2010;116(1):44–9.

    Article  CAS  PubMed  Google Scholar 

  41. No JH, et al. Expression of vascular endothelial growth factor and hypoxia inducible factor-1 alpha in cervical neoplasia. Ann N Y Acad Sci. 2009;1171:105–10.

    Article  CAS  PubMed  Google Scholar 

  42. Tang X, et al. Overexpression of human papillomavirus type 16 oncoproteins enhances hypoxia-inducible factor 1 alpha protein accumulation and vascular endothelial growth factor expression in human cervical carcinoma cells. Clin Cancer Res. 2007;13:2568–76.

    Article  CAS  PubMed  Google Scholar 

  43. Tewari KS, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014;370(8):734–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Penson RT, et al. Patient reported outcomes in a practice changing randomized trial of bevacizumab in the treatment of advanced cervical cancer: an NRG Oncology/Gynecologic Oncology Group study. Lancet Oncol. 2015;16(3):301–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. McLachlan J, et al. The impact of systemic therapy beyond first-line treatment for advanced cervical cancer. Clin Oncol. 2017;29:153–60.

    Article  CAS  Google Scholar 

  46. Chan JK, et al. Prognostic factors in neuroendocrine small cell cervical carcinoma. Cancer. 2003;97:568–74. American Cancer Society

    Article  PubMed  Google Scholar 

  47. Lee JM, et al. Prognostic factors in FIGO stage IB-IIA small cell neuroendocrine carcinoma of the uterine cervix treated surgically: results of a multi-center retrospective Korean study. Ann Oncol. 2008;19:321.

    Article  PubMed  Google Scholar 

  48. Silva EG, et al. Small cell carcinoma of the uterine cervix: pathology and prognostic factors. Surg Pathol. 1989;2:105–15.

    Google Scholar 

  49. Chan JK, et al. Prognostic factors in neuroendocrine small cell cervical carcinoma: a multivariate analysis. Cancer. 2003;97:568.

    Article  PubMed  Google Scholar 

  50. Cohen JG, et al. Small cell carcinoma of the cervix: treatment and survival outcomes of 188 patients. Am J Obstet Gynecol. 2010;203:347.e1.

    Article  Google Scholar 

  51. Chang TC, et al. Prognostic factors in surgically treated small cell cervical carcinoma followed by adjuvant chemotherapy. Cancer. 1998;83(4):712–8.

    Article  CAS  PubMed  Google Scholar 

  52. Zivanovic O, et al. Small cell neuroendocrine carcinoma of the cervix: analysis of outcome, recurrence pattern and the impact of platinum-based combination chemotherapy. Gynecol Oncol. 2009;112:590.

    Article  CAS  PubMed  Google Scholar 

  53. Eiriksson L, et al. Advancing fertility-sparing treatments in cervical cancer: where is the limit? Gynecol Oncol. 2012;126(3):317–8.

    Article  PubMed  Google Scholar 

  54. Lissoni AA, et al. A phase II, randomized trial of neo-adjuvant chemotherapy comparing a three-drug combination of paclitaxel, ifosfamide, and cisplatin (TIP) versus paclitaxel and cisplatin (TP) followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the Snap-02 Italian collaborative study. Ann Oncol. 2009;20(4):660–5.

    Article  CAS  PubMed  Google Scholar 

  55. Li R, et al. Prognostic value of responsiveness of neoadjuvant chemotherapy before surgery for patients with stage IB2/IIA2 cervical cancer. Gynecol Oncol. 2013;128(3):524–9.

    Article  CAS  PubMed  Google Scholar 

  56. NACCCMA Collaboration, Tierney JF. Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy for locally advanced cervical cancer: a systematic review and meta-analysis of individual patient data from 21 randomised trials. Eur J Cancer. 2003;39(17):2470–86.

    Google Scholar 

  57. Eddy GL, et al. Treatment of (“bulky”) stage IB cervical cancer with or without neoadjuvant vincristine and cisplatin prior to radical hysterectomy and pelvic/para-aortic lymphadenectomy: a phase III trial of the Gynecologic Oncology group. Gynecol Oncol. 2007;106(2):362–9.

    Article  CAS  PubMed  Google Scholar 

  58. Mossa B, et al. Follow-up in a long term randomized trial with neoadjuvant chemotherapy for squamous cell cervical carcinoma. Eur J Gynaecol Oncol. 2010;31(5):497–503.

    CAS  PubMed  Google Scholar 

  59. Dueñas-Gonzalez A, et al. A phase II study of multimodality treatment for locally advanced cervical cancer: neoadjuvant carboplatin and paclitaxel followed by radical hysterectomy and adjuvant cisplatin chemoradiation. Ann Oncol. 2003;14(8):1278–84.

    Article  PubMed  Google Scholar 

  60. Lissoni AA, et al. A phase II, randomized trial of neo-adjuvant chemotherapy comparing a three-drug combination of paclitaxel, ifosfamide, and cisplatin (TIP) versus paclitaxel and cisplatin (TP) followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the Snap-02 Italian collaborative study. Ann Oncol. 2009;20(4):660–5.

    Article  CAS  PubMed  Google Scholar 

  61. Kim HS, et al. Efficacy of neoadjuvant chemotherapy in patients with FIGO stage IB1 to IIA cervical cancer: an international collaborative meta-analysis. Eur J Surg Oncol. 2013;39(2):115–24.

    Article  CAS  PubMed  Google Scholar 

  62. McCormack M, et al. A phase II study of weekly neoadjuvant chemotherapy followed by radical chemoradiation for locally advanced cervical cancer. Br J Cancer. 2013;108(12):2464–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. clinicaltrials.gov NCT01566240 INTERLACE – induction chemotherapy plus chemo-radiation as first line treatment for locally advanced cervical cancer. https://clinicaltrials.gov/ct2/show/NCT01566240?term=NCT01566240&rank=1

  64. Dueñas-González A, et al. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011;29:1678.

    Article  PubMed  Google Scholar 

  65. Tangjitgamol S, et al. Adjuvant chemotherapy after concurrent chemoradiation for locally advanced cervical cancer. Cochrane Database Syst Rev. 2014;12:CD010401.

    Google Scholar 

  66. International Randomised Study (Australia and USA) OUTBACK trial sponsored by GOG and RCOG. http://www.rtog.org/LinkClick.aspx?fileticket=lU6JlzhBt7s%3d&tabid=290

  67. Hanahan D, et al. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  CAS  PubMed  Google Scholar 

  68. Lawrence M, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499:214–8. PMID: 23770567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Melsheimer P, et al. DNA aneuploidy and integration of human papillomavirus type 16 E6/E7 oncogenes in intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix uteri. Clin Cancer Res. 2004;10:3059–63.

    Article  CAS  PubMed  Google Scholar 

  70. Kanaan H, et al. Are virus-induced cancers more sensitive to checkpoint inhibitors? Future Oncol. 2016;12(23):2665–8.

    Article  CAS  PubMed  Google Scholar 

  71. clinicaltrials.gov NCT02488759 CheckMate358 – a study to investigate the safety and efficacy of Nivolumab in virus-associated tumors. https://clinicaltrials.gov/ct2/show/NCT02488759?term=NCT02488759&rank=1

  72. Clinicaltrials.gov NCT02834013 Nivolumab and Ipilimumab in treating patients with rare tumors. https://clinicaltrials.gov/ct2/show/NCT02834013?term=NCT02834013&rank=1

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Authors and Affiliations

  1. Department of Clinical Oncology/Radiotherapy, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK

    Romelie Rieu

  2. Department of Clinical Oncology/Radiotherapy, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK

    Gemma Eminowicz

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  1. Romelie Rieu
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Correspondence to Gemma Eminowicz .

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  1. The Joan and Sanford I. Weill Medical College/Graduate School of Medical Sciences, The New York Presbyterian Hospital-Weill Cornell Medical Center, and Sandra and Edward Meyer Cancer Center, Cornell University, New York, NY, USA

    Samir A. Farghaly

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Rieu, R., Eminowicz, G. (2019). Chemotherapy for Cervical Cancer. In: Farghaly, S. (eds) Uterine Cervical Cancer. Springer, Cham. https://doi.org/10.1007/978-3-030-02701-8_12

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