Abstract
Radiation therapy has been the most active agent for the treatment of patients with locally advanced cervical cancer for many years. Chemotherapy has shown some activity, but data has been lacking to support its routine use. Recently, data from five prospective, randomized trials evaluating this difficult population have matured. Reports from these trials are startlingly similar, leading to the common conclusion that concurrent cisplatin chemotherapy and radiation therapy substantially decrease the risk of relapse and increase the overall survival. These results are compelling evidence for the inclusion of cisplatin with irradiation as a new standard of care for patients with locally advanced cervical cancer.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References and Recommended Reading
Landis SH, Murray T, Bolden S, et al.: Cancer statistics 1998. Ca Cancer J Clin 1998, 48:6–29.
Fu KK: Biological basis for the interaction of chemotherapeutic agents and radiation therapy. Cancer 1985, 55:2123–2130.
Perez CA, Grigsby PW, Chao CK, et al.: Chemotherapy and irradition in locally advanced squamous cell carcinoma of the uterine cervix: a review. Semin Radiat Oncol 1997, 7 (suppl 2):45–65.
Potchen EJ, Kinzie J, Curtis C, et al.: Effect of irradiation on tumor microvascular permeability to macromolecules. Cancer 1972, 20:639–642.
Thigpen T, Vance RB, Balducci L, et al.: Chemotherapy in the management of advanced or recurrent cervical and endometrial carcinoma. Cancer 1981, 48:658–665.
Cummings BJ, Rider WR, Harwood AR, et al.: Combined radical radiation therapy and chemotherapy for primary squamous cell carcinoma of the anal canal. Cancer Treat Rep 1982, 66:489–492.
Herskovic A, Martz K, al-Sarraf M, et al.: Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 1992, 226:1593–1598.
Stupp R, Weichselbaum R, Vokes E: Combined modality therapy of head and neck cancer. Semin Oncol 1994, 21:349–358.
Sinclair W: Hydroxyurea: differential lethal effects on cultured mammalian cells during the cell cycle. Science 1965, 150:1729–1731.
Hreschyshyn MM, Aron BS, Boronow RC, et al.: Hydroxyurea or placebo combined with radiation to treat stages IIIB and IV cervical cancer confined to the pelvis. Int J Radiat Oncol Biol Phys Oncol 1979, 5:317–322.
Stehman FB, Bundy BN, Thomas G, et al.: Hydroxyurea versus misonidazole with radiation in cervical carcinoma: long term follow-up of a Gynecologic Oncology Group trial. J Clin Oncol 1993, 11:1523–1528.
Byfield JE, Calabro-Jones P, Klisak I, et al.: Pharmacologic requirements for obtaining sensitization of human tumor cells in vitro to combined 5-flurouracil or ftorafur and x rays. Int J Radiat Oncol Biol Phys 1982, 8:1923–1933.
Thomas G, Dembo A, Beale F, et al.: Concurrent radiation, mitomycin C and 5-fluorouracil in poor prognosis carcinoma of the cervix: Preliminary results of a phase I-II study. Int J Radiat Oncol Biol Phys 1984, 10:1785–1790.
Thomas G, Dembo A, Fyles A, et al.: Concurrent chemoradiation in advanced cervical cancer. Gynecol Oncol 1990, 38:446–451.
Thomas G, Dembo A, Ackerman I, et al.: A randomized trial of standard versus partially hyperfractionated radiation with or without concurrent 5-fluorouracil in locally advanced cervical cancer. Gynecol Oncol 1998, 69:137–145.
Bonomi P, Blessing JA, Stehman FB, et al.: Randomized trial of three cisplatin dose schedules in squamous cell carcinoma of the cervix. J Clin Oncol 1985, 3:1079–1085.
Twiggs LB, Potish RA, Mcintyre S, et al.: Concurrent weekly cis-platinum and radiotherapy in advanced cervical cancer: a preliminary dose escalating toxicity study. Gynecol Oncol 1986, 24:143–148.
Monyak DJ, Twiggs LB, Potish RA, et al.: Tolerance and preliminary results of simultaneous therapy with radiation and cisplatin for advanced cervical cancer. NCI Monogr 1988, 6:369–373.
Malfetano JH, Keys H: Aggressive multimodality treatment for cervical cancer with para-aortic lymph node metastasis. Gynecol Oncol 1991, 42:44–47.
Malfetano JH, Keys H, Kredentser D, et al.: Weekly cisplatin and radical radiation therapy for advanced, recurrent and poor prognosis cervical carcinoma. Cancer 1993, 71:3703–3706.
Malfetano JH, Keys, H, Cunningham MJ, et al.: Extended field radiation and cisplatin for stage IIB and IIIB cervical cancer. Gynecol Oncol 1997, 67:203–207.
Runowicz CD, Wadler S, Rodriguez LR, et al.: Concomitant cisplatin and radiotherapy in locally advanced cervical carcinoma. Gynecol Oncol 1989, 34:395–401.
Begg AC: Cisplatin and radiation: Interaction probabilities and therapeutic possibilities. Int J Radiat Oncol Biol Phys 1990, 19:1183–1189.
Goolsby CD, Daly JW, Skinner OD, et al.: Combination of 5-fluorouracil and radiation as primary therapy of carcinoma of the cervix. Obstet Gynecol 1968, 32:674–676.
Ludgate SM, Crandon AJ, Hudson CN, et al.: Synchronous 5-fluorouracil, mitomycin-c and radiation therapy in the treatment of locally advanced carcinoma of the cervix. Int J Radiat Oncol Biol Phys 1988, 15:893–899.
Heaton D, Yordan E, Reddy S, et al.: Treatment of 29 patients with bulky squamous cell carcinoma of the cervix with simultaneous cisplatin, 5-fluoracil, and split-course hyperfractionated radiation therapy. Gynecol Oncol 1990, 38:323–327.
Roberts WS, Kavanagh JJ, Greenberg H, et al.: Concomitant radiation therapy and chemotherapy in the treatment of advanced squamous carcinoma of the lower female genital tract. Gynecol Oncol 1989, 34:183–186.
Kuske RR, Perez CA, Grigsby PW, et al.: Phase I/II study of definitive radiotherapy and chemotherapy (cisplatin and 5-fluorouracil) for advanced and recurrent gynecologic malignancies. Am J Clin Oncol 1989, 12:467–473.
National Cancer Institute: Concurrent chemoradiation for cervical cancer. Clinical Announcement. Washington, DC: National Cancer Institute; February 22, 1999.
Whitney CW, Sause W, Bundy BN, et al.: A randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stages IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol 1999, 17:1339–1348. In this study, patients with stage IIB to IVA cervical cancer, negative para-aortic lymph nodes, and pelvic washings were randomized to receive pelvic radiotherapy concurrently with either hydroxyurea or combined 5-FU and cisplatin. The relative risk of both progressionfree survival and overall survival was significantly in favor of the group receiving cisplatin. Sites of progression were not significantly different between the two groups, and toxicity was acceptable.
Keys HM, Bundy BN, Stehman FB, et al.: Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 1999, 340:1154–1161. Patients with bulky stage IB cervical cancer greater than or equal to 4 cm were randomized to radiation alone versus concurrent radiation and weekly cisplatin chemotherapy. Both groups received posttreatment hysterectomy. The relative risk of death in the combined therapy group compared to the group given radiation alone was 0.54. The authors concluded that adding weekly infusions of cisplatin to pelvic radiotherapy followed by hysterectomy significantly reduced the risk of disease recurrence and death in women with bulky stage IB cervical cancers.
Rose PG, Bundy BN, Watkins EB, et al.: Concurrent cisplatinbased radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 1999, 340:1144–1153. Report on a study in which patients with stage IIB to IVA cervical cancer and negative para-aortic lymph nodes were randomized to one of three treatment arms. The control arm, radiation therapy with concurrent hydroxyurea, was compared with radiation plus cisplatin and radiation plus cisplatin, 5-FU, and hydroxyurea. Both cisplatincontaining arms showed similar improvements in survival rate and progression-free survival. Patients receiving cisplatin alone had lower toxicity than those receiving the multidrug regimen.
Morris M, Eifel PJ, Lu J, et al.: Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med 1999, 340:1137–1143.
Peters WA III, Liu PY, Barrett R, et al.: Cisplatin, 5-flurouracil plus radiation therapy are superior to radiation therapy as adjunctive therapy in high-risk, early-stage carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: report of a phase III inter-group study [abstract]. Gynecol Oncol 1999, 72:443. In this study, patients with stage IIB to IVA cervical cancer, negative para-aortic lymph nodes, and pelvic washings were randomized to receive pelvic radiotherapy concurrently with either hydroxyurea or combined 5-FU and cisplatin. The relative risk of both progressionfree survival and overall survival was significantly in favor of the group receiving cisplatin. Sites of progression were not significantly different between the two groups, and toxicity was acceptable.
Stehman FB, Bundy BN, DiSaia PJ, et al.: Carcinoma of the cervix treated with irradiation therapy I: a multivariate analysis of prognostic variables in the Gynecologic Oncology Group. Cancer 1991, 67:2776–2785.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schilder, J.M., Stehman, F.B. Concurrent chemotherapy and radiation therapy in primary cancer of the cervix. Curr Oncol Rep 1, 41–46 (1999). https://doi.org/10.1007/s11912-999-0008-4
Issue Date:
DOI: https://doi.org/10.1007/s11912-999-0008-4