A Randomized Phase III Study Comparing Concurrent Gemcitabine plus Cisplatin and Radiation followed by Adjuvant Gemcitabine plus Cisplatin versus Concurrent Cisplatin and Radiation in Patients with Stage IIB to IVA Carcinoma of the Cervix
Carolyn Vachani, RN, MSN, AOCN
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 18, 2009
Title: A Randomized Phase III Study Comparing Concurrent Gemcitabine plus Cisplatin and Radiation followed by Adjuvant Gemcitabine plus Cisplatin versus Concurrent Cisplatin and Radiation in Patients with Stage IIB to IVA Carcinoma of the Cervix
Reviewer: Christine Hill-Kayser, MD
Presenter: Alfonso Duenas-Gonzalez
Affiliation: Unidad de Investigacion Biomédica en Cįncer, Mexico City, Mexico
Locally advanced cervical cancer (stage IIB-IVA) is most commonly treated with radiation (usually a combination of external beam andbrachytherapy) and cisplatin, given weekly. Despite this aggressive treatment, 5-year overall survival in the U.S. is only 55%. This study compared the standard regimen to the sameregimen with the addition of gemcitabine. The addition of gemcitabine has two advantages: it introduces another chemotherapy drug with different activity from cisplatin, and gemcitabine is a radiosensitizer, hopefully making the tissues more sensitive to the radiation damage.
259 participants received gemcitabine + cisplatin (GC), and 256 received cisplatin (C), along with external beam radiation and brachytherapy. In addition, the GC group also received 2 additional chemotherapy cycles after radiation (76% completed both doses). Of note, this trial took place in Mexico, and patients came from 7 different countries. The number of patients with each stage of disease was: IIB (n = 316), IIIA (n = 2), IIIB (n = 188), IVA (n = 9). The GC arm had statistically significant advantages in progression-free survival (74.4% vs. 65%) and overall survival (78.2% vs. 69.1%) at 3 years. The GC group was also less likely to develop a distant metastasis (in another organ): 21 patients versus 42 in the C group.
As you might guess, the GC group also had many more side effects. These included 2 deaths related to treatment (0 in the C group), and 33 side effects deemed “serious” (versus 12 in C group). These side effects included decreased blood counts, diarrhea, vomiting and proctitis (all more common in the GC group).
This trial presents compelling results for the addition of gemcitabine to the standard regimen. However, two previous trials combining gemcitabine with radiation in cervical cancer were stopped due to unacceptable toxicity levels. While we want to improve cancer-related survival among these patients, it should not be at the cost of deaths due to treatment. It may be beneficial for future trials to give gemcitabine before and/or after radiation or with lower radiation doses to limit toxicity.
Also see Interpreting a Cancer Research Study