Cisplatin and radiation improve DFS in stage IIIB cervical cancer

ATLANTA – Women with advanced cervical cancer who received cisplatin in addition to external-beam radiation and brachytherapy had slightly but significantly better disease-free survival than women who received radiation alone, according to a study by Dr. Antonio Zuliani of Campinas State University in Campinas, Brazil, and his colleagues.

In a randomized controlled trial involving 147 women with stage IIIB epidermoid cervical cancer, the hazard ratio for disease-free survival (DFS) with the addition of cisplatin was 0.52 compared with radiation alone (P = .04). There was no significant difference in overall survival (OS), however, Dr. Zuliani said at the annual meeting of the American Society for Radiation Oncology.

"The association of chemotherapy to radiotherapy was beneficial regarding disease-free survival of women with cervical cancer stage IIIB, but overall survival was not statistically significant. The toxicity of the combined treatment was not greater than that resulting from radiotherapy alone," Dr. Zuliani said.

He pointed to a meta-analysis of 18 clinical trials published in 2010, which suggested that chemoradiotherapy offered about a 10% 5-year benefit in DFS and OS for women with stage IB-IIA disease but only about a 3% advantage for women with stage IIIB disease, although the difference was not significant.

To see whether chemoradiotherapy could benefit patients with more advanced disease, the authors randomly assigned 75 women to receive 45 Gy external beam radiation therapy (EBRT) in 25 fractions to the pelvic region, with a 14.4-Gy boost to compromised parametria, and high dose-rate brachytherapy in four weekly 7-Gy fractions delivered to the crossing point of the uterine artery and ureter. An additional 72 women were assigned to receive the same radiation protocol plus weekly cisplatin at 40 mg/m² concurrent with EBRT.

After a mean follow-up of 54.9 months, 43 women in the cisplatin group (60%) were alive without disease progression, compared with 40 (53%) in the radiation-only group. The mean DFS was significantly worse for women with Karnofsky Performance Scale scores less than 90 (relative risk [RR], 2.52; P = .01), for women with bilateral wall invasion (RR, 2.93; P = .02), and for those whose baseline hemoglobin (Hb) was below 10 mg/dL (RR, 2.22; P = .04).

Mean OS also was worse among women with Karnofsky scores less than 90 (RR, 2.75) and baseline Hb below 10 mg/dL (RR, 2.82; P = .01).

There were 29 deaths (40%) in the cisplatin group and 35 (46%) in the radiation-only arm. Deaths from disease recurrence occurred in 25 (34%) women treated with cisplatin and 32 (42%) women treated with radiation only.

Acute grade 1 or 2 acute toxicities (Cooperative Group Common Toxicity Criteria of the Radiation Oncology Therapy Group) occurred in 37.5% of patients who received cisplatin, compared with 28% of those who received radiation alone; the difference was not significant. Late grade 3 or 4 toxicities were 9.7% and 3%, respectively (not significant).

Dr. Zuliani did not disclose the funding source for the study but reported having no conflicts of interest.

ATLANTA – Women with advanced cervical cancer who received cisplatin in addition to external-beam radiation and brachytherapy had slightly but significantly better disease-free survival than women who received radiation alone, according to a study by Dr. Antonio Zuliani of Campinas State University in Campinas, Brazil, and his colleagues.

In a randomized controlled trial involving 147 women with stage IIIB epidermoid cervical cancer, the hazard ratio for disease-free survival (DFS) with the addition of cisplatin was 0.52 compared with radiation alone (P = .04). There was no significant difference in overall survival (OS), however, Dr. Zuliani said at the annual meeting of the American Society for Radiation Oncology.

"The association of chemotherapy to radiotherapy was beneficial regarding disease-free survival of women with cervical cancer stage IIIB, but overall survival was not statistically significant. The toxicity of the combined treatment was not greater than that resulting from radiotherapy alone," Dr. Zuliani said.

He pointed to a meta-analysis of 18 clinical trials published in 2010, which suggested that chemoradiotherapy offered about a 10% 5-year benefit in DFS and OS for women with stage IB-IIA disease but only about a 3% advantage for women with stage IIIB disease, although the difference was not significant.

To see whether chemoradiotherapy could benefit patients with more advanced disease, the authors randomly assigned 75 women to receive 45 Gy external beam radiation therapy (EBRT) in 25 fractions to the pelvic region, with a 14.4-Gy boost to compromised parametria, and high dose-rate brachytherapy in four weekly 7-Gy fractions delivered to the crossing point of the uterine artery and ureter. An additional 72 women were assigned to receive the same radiation protocol plus weekly cisplatin at 40 mg/m² concurrent with EBRT.

After a mean follow-up of 54.9 months, 43 women in the cisplatin group (60%) were alive without disease progression, compared with 40 (53%) in the radiation-only group. The mean DFS was significantly worse for women with Karnofsky Performance Scale scores less than 90 (relative risk [RR], 2.52; P = .01), for women with bilateral wall invasion (RR, 2.93; P = .02), and for those whose baseline hemoglobin (Hb) was below 10 mg/dL (RR, 2.22; P = .04).

Mean OS also was worse among women with Karnofsky scores less than 90 (RR, 2.75) and baseline Hb below 10 mg/dL (RR, 2.82; P = .01).

There were 29 deaths (40%) in the cisplatin group and 35 (46%) in the radiation-only arm. Deaths from disease recurrence occurred in 25 (34%) women treated with cisplatin and 32 (42%) women treated with radiation only.

Acute grade 1 or 2 acute toxicities (Cooperative Group Common Toxicity Criteria of the Radiation Oncology Therapy Group) occurred in 37.5% of patients who received cisplatin, compared with 28% of those who received radiation alone; the difference was not significant. Late grade 3 or 4 toxicities were 9.7% and 3%, respectively (not significant).

Dr. Zuliani did not disclose the funding source for the study but reported having no conflicts of interest.

ATLANTA – Women with advanced cervical cancer who received cisplatin in addition to external-beam radiation and brachytherapy had slightly but significantly better disease-free survival than women who received radiation alone, according to a study by Dr. Antonio Zuliani of Campinas State University in Campinas, Brazil, and his colleagues.

In a randomized controlled trial involving 147 women with stage IIIB epidermoid cervical cancer, the hazard ratio for disease-free survival (DFS) with the addition of cisplatin was 0.52 compared with radiation alone (P = .04). There was no significant difference in overall survival (OS), however, Dr. Zuliani said at the annual meeting of the American Society for Radiation Oncology.

"The association of chemotherapy to radiotherapy was beneficial regarding disease-free survival of women with cervical cancer stage IIIB, but overall survival was not statistically significant. The toxicity of the combined treatment was not greater than that resulting from radiotherapy alone," Dr. Zuliani said.

He pointed to a meta-analysis of 18 clinical trials published in 2010, which suggested that chemoradiotherapy offered about a 10% 5-year benefit in DFS and OS for women with stage IB-IIA disease but only about a 3% advantage for women with stage IIIB disease, although the difference was not significant.

To see whether chemoradiotherapy could benefit patients with more advanced disease, the authors randomly assigned 75 women to receive 45 Gy external beam radiation therapy (EBRT) in 25 fractions to the pelvic region, with a 14.4-Gy boost to compromised parametria, and high dose-rate brachytherapy in four weekly 7-Gy fractions delivered to the crossing point of the uterine artery and ureter. An additional 72 women were assigned to receive the same radiation protocol plus weekly cisplatin at 40 mg/m² concurrent with EBRT.

After a mean follow-up of 54.9 months, 43 women in the cisplatin group (60%) were alive without disease progression, compared with 40 (53%) in the radiation-only group. The mean DFS was significantly worse for women with Karnofsky Performance Scale scores less than 90 (relative risk [RR], 2.52; P = .01), for women with bilateral wall invasion (RR, 2.93; P = .02), and for those whose baseline hemoglobin (Hb) was below 10 mg/dL (RR, 2.22; P = .04).

Mean OS also was worse among women with Karnofsky scores less than 90 (RR, 2.75) and baseline Hb below 10 mg/dL (RR, 2.82; P = .01).

There were 29 deaths (40%) in the cisplatin group and 35 (46%) in the radiation-only arm. Deaths from disease recurrence occurred in 25 (34%) women treated with cisplatin and 32 (42%) women treated with radiation only.

Acute grade 1 or 2 acute toxicities (Cooperative Group Common Toxicity Criteria of the Radiation Oncology Therapy Group) occurred in 37.5% of patients who received cisplatin, compared with 28% of those who received radiation alone; the difference was not significant. Late grade 3 or 4 toxicities were 9.7% and 3%, respectively (not significant).

Dr. Zuliani did not disclose the funding source for the study but reported having no conflicts of interest.