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Adding chemotherapy improves survival in cervical cancer

BMJ 1999; 318 doi: https://doi.org/10.1136/bmj.318.7184.623 (Published 06 March 1999) Cite this as: BMJ 1999;318:623
  1. Deborah Josefson,
  2. San Francisco

    Cervical cancer survival rates could increase by up to 50%if chemotherapy were added to standard treatment regimens, according to an announcement issued last week by the US National Cancer Institute.

    The National Cancer Institute took the unusual step of a sending a clinical alert to 20000 oncologists after reviewing the preliminary results of five separate phase III studies. All of the studies showed that the addition of cisplatin based chemotherapy to radiation treatment improved survival rates for locally invasive cervical cancer by 30-50%The director of the institute, Dr Richard Klausner, said that the results of the five studies were remarkably consistent and that cumulatively the findings are “likely to change the standard of care for cervical cancer.”

    Each of the trials enrolled several hundred patients; 1912 women were enrolled overall. Three of the studies will be published in the 15 April edition of the New England Journal of Medicine and the other two will be reported at the San Francisco meeting of the Society of Gynecologic Oncologists (22 March). The journal has posted an early release of the three papers on its website (www.nejm.org) because of the public health implications of the findings.

    Until now, locally and regionally invasive cervical cancer has been treated with surgery and pelvic irradiation. The new research suggests that a radical revision of this treatment may be required. In three of the trials, women were randomly allocated to groups that received either radiation treatment alone or radiation plus concomitant chemotherapy. Chemotherapy was started within 16 hours of radiation treatment. The chemotherapeutic regimens used included cisplatin, hydroxyurea, and 5-fluorouracil. All three trials found that those patients randomly allocated to chemotherapy plus radiation had higher survival rates than those treated with radiation therapy alone.

    Researchers suggested that a synergistic effect may be occurring when chemotherapy is combined with radiotherapy. The addition of chemotherapeutic agents may prevent cancerous cells from repairing DNA damaged by radiation and may further cripple the cancer cells' replicative ability. Commenting on the studies, Dr Edward Trimble of the National Cancer Institute suggested that cisplatin based regimens had the potential to save thousands of lives a year. He said: “This should be the new standard of care. There is no reason why it can't be, because these treatments are available in every cancer centre in the country.


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    Cervical cancer survival is improved when cisplatin chemotherapy is part of treatment

    Three trials of treating cervical cancer by adding chemotherapy to standard treatment

    • The trial led by Dr Peter Rose (of Case Western University School of Medicine in Cleveland, Ohio) included 526 women with stage IIb, III, or IVa primary untreated invasive squamous or adenosquamous cervical carcinoma. The women were randomly allocated to treatment with radiotherapy in combination with one of three concurrent chemotherapy regimens: cisplatin alone, hydroxyurea alone, or cisplatin and 5-fluorouracil together. The primary endpoints were survival and progression free survival.

    • The study led by Dr Mitchell Morris (of University of Texas MD Anderson Cancer Center in Houston) compared treatment with radiotherapy alone to treatment with radiation plus cisplatin and 5-fluorouracil in 388 patients with stage IIb, III, and IVa cervical cancer.

    • The trial led by Dr Henry Keys (of Albany Medical College in New York) compared treatment with cisplatin plus radiotherapy to radiotherapy alone in 369 women with bulky, stage Ib cervical cancers. Adjuvant hysterectomy was performed in all women.

    • So far, half of the patients have been followed for about 36 months, and 83%of the women who received chemotherapy are alive, compared with only 74%of those treated with radiation alone.

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