Serum nucleosomes during neoadjuvant chemotherapy in patients with cervical cancer. Predictive and prognostic significance.
BACKGROUND
It has been shown that free DNA circulates in serum plasma of patients with cancer and that at least part is present in the form of oligo- and monucleosomes, a marker of cell death. Preliminary data has shown a good correlation between decrease of nucleosomes with response and prognosis. Here, we performed pre- and post-chemotherapy determinations of serum nucleosomes with an enzyme-linked immunosorbent assay (ELISA) method in a group of patients with cervical cancer receiving neoadjuvant chemotherapy.


METHODS
From December 2000 to June 2001, 41 patients with cervical cancer staged as FIGO stages IB2-IIIB received three 21-day courses of carboplatin and paclitaxel, both administered at day 1; then, patients underwent radical hysterectomy. Nucleosomes were measured the day before (baseline), at day seven of the first course and day seven of the third course of chemotherapy. Values of nucleosomes were analyzed with regard to pathologic response and to time to progression-free and overall survival.


RESULTS
All patients completed chemotherapy, were evaluable for pathologic response, and had nucleosome levels determined. At a mean follow-up of 23 months (range, 7-26 months), projected progression time and overall survival were 80.3 and 80.4%, respectively. Mean differential values of nucleosomes were lower in the third course as compared with the first course (p >0.001). The decrease in the third course correlated with pathologic response (p = 0.041). Survival analysis showed a statistically significant, better progression-free and survival time in patients who showed lower levels at the third course (p = 0.0243 and p = 0.0260, respectively). Cox regression analysis demonstrated that nucleosome increase in the third course increased risk of death to 6.86 (95% confidence interval [CI 95%], 0.84-56.0).


CONCLUSIONS
Serum nucleosomes may have a predictive role for response and prognostic significance in patients with cervical cancer patients treated with neoadjuvant chemotherapy.
Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología e Instituto de Investigaciones Biomédicas (IIB/INCan), Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico. ctrejo@salud.gob.mx
Catalina
C
Trejo-Becerril
Luis F
LF
Oñate-Ocaña
Lucía
L
Taja-Chayeb
América
A
Vanoye-Carlo
Lucely
L
Cetina
Alfonso
A
Duenas-Gonzalez
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D016001:Confidence Intervals; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007044:Hysterectomy / Q000379:methods; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009707:Nucleosomes / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery
D014408:Biomarkers, Tumor; D009707:Nucleosomes; D016190:Carboplatin; D017239:Paclitaxel