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Key Words

Cervical cancer, cisplatin (Platinol®); hydroxyurea. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)

Summary

Women with cervical cancer that had spread locally or regionally who received the chemotherapy drug cisplatin in addition to radiation therapy lived significantly longer than women who received the drug hydroxyurea in addition to radiation therapy.

Source

Journal of Clinical Oncology, published online May 14, 2007; in print July 1, 2007 (see the journal abstract)
(J Clin Oncol. 2007 May 14; [Epub ahead of print])

Background

In 1999, the results of five randomized clinical trials showed that adding cisplatin-based chemotherapy to radiation therapy (chemoradiation) for the treatment of cervical cancer that has spread locally (in the cervix or its immediate vicinity) or regionally (within the pelvis) improves survival compared to treatment with radiation therapy alone. In response to these results, the National Cancer Institute (NCI) released a clinical announcement to doctors recommending the use of chemoradiation for women with locally or regionally advanced cervical cancer.

The release of the clinical announcement greatly increased the number of women who received chemoradiation for cervical cancer. However, several questions remained about this treatment regimen. The 1999 studies only included a few years of follow-up, leading some doctors to wonder if long-term side effects would be worse in women who receive chemotherapy in addition to radiation therapy. In addition, the early results did not conclusively show if chemoradiation benefited women with more advanced regional disease over the long term as much as women whose disease was more localized.

To help answer these questions, investigators from one of the five trials published in 1999 performed an analysis based on data from participating women who had been followed for an average of almost nine years.

The Study

The original randomized trial performed by the Gynecologic Oncology Group, called GOG 120, enrolled women with locally or regionally advanced cervical cancer. The investigators randomly assigned participating women to one of three groups. One group received the chemotherapy drug cisplatin alone, the second received the chemotherapy drug hydroxyurea alone, and the third received a combination of cisplatin, hydroxyurea, and the chemotherapy drug 5-fluorouracil (see the protocol summary).

All drugs were given during radiation therapy, and all women in the three groups received the same type and amount of radiation therapy. The investigators recorded the incidence of early and late side effects, and compared progression-free survival (survival without evidence of tumor growth) and overall survival among the three groups.

The study’s lead author was Peter G. Rose, M.D., from the Cleveland Clinic Foundation in Cleveland, Ohio.

Results

Between 1992 and 1997, 176 women received cisplatin alone, 177 received hydroxyurea alone, and 173 received cisplatin, 5-flurouracil, and hydroxyurea. In this longer-term analysis, patients were followed for an average of almost nine years.

Women who received either cisplatin or the combination of cisplatin, 5-flurouracil, and hydroxyurea had significantly longer progression-free survival than women who received hydroxyurea alone.

• At 30 months of follow-up, 63 percent of women given cisplatin and 62 percent given the combination were alive without progression of disease, compared to 42 percent of women given hydroxyurea.
• At five years of follow-up, 58 percent of women given cisplatin and 57 percent given the combination were alive without progression of disease, compared to 35 percent of women given hydroxyurea
• At 10 years of follow-up, 46 percent of women given cisplatin and 43 percent given the combination were alive without progression of disease, compared to 26 percent of women given hydroxyurea.

Overall survival was also greater for women who received cisplatin or the combination of cisplatin, 5-flurouracil, and hydroxyurea.

• At 30 months of follow-up, 70 percent of women given cisplatin and 70 percent given the combination were alive, compared to 53 percent of women given hydroxyurea.
• At 5 years of follow-up, 60 percent of women given cisplatin and 61 percent given the combination were alive, compared to 40 percent of women given hydroxyurea.
• At 10 years of follow-up, 53 percent of women given cisplatin and 53 percent given the combination were alive, compared to 34 percent of women given hydroxyurea.

Cisplatin-based chemoradiation improved progression-free and overall survival for women regardless of whether the cancer had spread locally or regionally (more advanced cancer). After adjusting for the fact that more patients who received cisplatin or cisplatin, 5-flurouracil, and hydroxyurea were alive for the longer-term analysis of side effects, the investigators did not observe a statistically significant difference in late-occurring side effects between the groups.

Comments

“Collectively, this follow-up analysis continues to support the use of cisplatin-based concurrent chemotherapy with pelvic radiation therapy for locally advanced stage cervical cancer,” summarized the authors.

“This study shows the two things it attempted to show: that there is not an increase in toxicity…and that…we should use chemotherapy for advanced-stage disease as well as earlier-stage disease,” explained Herbert Kotz, M.D., adjunct investigator in the National Cancer Institute’s Medical Oncology Branch. “Cisplatin is currently the standard to which any other new treatment will be compared.”

This study only used a type of radiation therapy called whole pelvic irradiation, with additional brachytherapy (internal radiation therapy, in which radioactive material is placed into the vagina adjacent to the cervical cancer). But Kotz noted that some patients with cervical cancer – those whose disease has spread to the lymph nodes near the aorta, the body’s main artery – may benefit more from extended field radiation. More study is needed to determine whether chemoradiation with extended field radiation is tolerable and most effective for these patients.

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