Neoadjuvant and adjuvant chemotherapy of cervical cancer: mature results of the phase 2 PBM-PFU protocol.

Abstract

OBJECTIVE:

The mature results of the neoadjuvant and adjuvant chemotherapy arms of the nonrandomized, phase 2 Yale University cisplatin, bleomycin, methotrexate, and 5-FU protocol are presented.

METHODS:

Sixty-seven patients were prospectively accrued with a median follow-up of 5.4 years, and standard parameters of toxicity and efficacy were studied. Both univariate and multivariate analyses were applied.

RESULTS:

The 5-year disease-free survival of 78% for the 25 patients in the adjuvant group, of which 80% had high-risk features including positive margins, parametria, and lymph nodes and 28% had adenocarcinomas, was comparable to recent relevant literature. Only 64% of patients in this group received consolidation radiation therapy, which did not impact on survival. Only 12% of patients recurred distantly. Notably, those who received 4 months or more of chemotherapy had prolonged survival (P = 0.012). In the neoadjuvant group, chemotherapy response rate among 42 patients (with stages 1B-IIIB cancer) was 79% (50% partial response, 29% complete response), and no patient progressed. In the subgroup of 22 patients who underwent surgery after chemotherapy, 59% had nonsquamous histology. Forty-five percent of patients with stage IIB cancer were deemed operable after chemotherapy. Ninety-five percent received postoperative radiation therapy. There was a 9% pathologic complete response rate, with positive lymph nodes found in 27%. Notably, those who received 3 months or less of chemotherapy had improved overall survival (P = 0.030). Survival rates of these 22 patients at 3 and 5 years were 73% and 63%, respectively. Although not randomized, these survival rates were similar to those achieved with chemoradiation.

CONCLUSIONS:

Although there are several logistical/design features of the cisplatin, bleomycin, methotrexate, and 5-FU regimen that are not in line with the current chemotherapy era, our experience with this well-tolerated regimen can serve as a proof of principle. Our data suggests that both neoadjuvant and adjuvant cisplatin-based neoadjuvant chemotherapy may have their place. It also raises the possibility that the optimal duration of chemotherapy in adjuvant cases should be longer than in neoadjuvant cases.

• Authors: Rebecca McCaffrey, Mert Bahtiyar, Ernest I Kohorn, Joseph T Chambers, Peter E Schwartz, Setsuko K Chambers
• Journal: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (Int J Gynecol Cancer) Vol. 21 Issue 3 Pg. 535-44 (Apr 2011) ISSN: 1525-1438 [Electronic] England
• PMID: 21436702 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

• Bleomycin
• Cisplatin
• Leucovorin
• Fluorouracil
• Methotrexate

Topics

• Adenocarcinoma (drug therapy)
• Adult
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bleomycin (therapeutic use)
• Carcinoma, Adenosquamous (drug therapy)
• Carcinoma, Squamous Cell (drug therapy)
• Chemotherapy, Adjuvant
• Cisplatin (therapeutic use)
• Female
• Fluorouracil (therapeutic use)
• Humans
• Leucovorin (therapeutic use)
• Maximum Tolerated Dose
• Methotrexate (therapeutic use)
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Recurrence, Local (drug therapy)
• Neoplasm Staging
• Prospective Studies
• Survival Rate
• Treatment Outcome
• Uterine Cervical Neoplasms (drug therapy)
• Young Adult