Neoadjuvant Chemotherapy for Early Stage Cervical Cancer

Hilman Tadjoedin

Division of Hematology-Medical Oncology, Department of Internal Medicine,School of Medicine – Dharmais National Cancer Centre

Presented at HUT – RSKD, Audiotorium RSKD, November 9th 2010

Introduction :

• In the past 10 years : strategy of neoadjuvant chemotherapy (CT) → surgery +/- RT : great interest in cervical cancer (CC).

• Cispatine-based CT previously untreated locally advanced CC : high response rate.

• Few cases bulky early stage (IB - IIA ) : are included; long-term survival and complications are unknown due to short follow-up.

Introduction :

• Sardi et al : interim analysis of a prospective (including : sizable number of bulky stage IB).

• Unfortunately the design has been criticized :

1. Criteria of bulky

2. Lack of stratification of prognostic factors

3. Using 2 or 3 modalities → concern of overtreatment

• The course of PVB (cisplatin,vinblastin and bleomycin) is attractive in short recycling time → minimizing the possible accelerated repopulation of cancer cells.

Percentage of total Dollars by scientific area spent on Cervical Cancer FY 2002

Cervical Cancer mortality rates by country : 1970 - 1998

• Between 1988-1991 : bulky mass CC, treated at CGMH, with PVB neoadjuvant CT.

• Fifty-nine evaluable pts. : 51 (HT) vs 8 (definitive RT).

• Overall clinical response : 81,4%, CR : 18,6%.

• Clinical response to CT, not different by : stage, histologic type, tumor size, level of squamous cell antigen or DNA ploidy; but tumor with high DNA indices (DI) > 1,3 higher clinical response rate.

• Five-year survival rate pts. with HT : 80,3%, 1 vs 8 survived; 7 pts. → poor clinical response : 2 node meta’sand 3 died; 4 pts. dettered HT for poor response died.

• This study : the value of DNA flowcytometry in predicting chemosensitive.

Discussion :

• Confirmed preliminary results → high objective RR : 81,4% & acceptable acute toxicities.

• In this series : clinical response to CT wasn’t different by :

1. stage : IB or IIA

2. histologic type : squamous / non

3. tumor size : 4-7 cm

4. level of SCC antigen

5. courses of CT

6. DNA ploidy

• However : tumors with DI (DNA Index > 1,3 higher clinical RR, than with ≤ 1,3.

Discussion :

• Residual tumor size and grade of histological response : significantly related to clinical response, while :

1. Parametrial extension

2. Lymph node status weren’t.

3. Lymphatic permeation

• Clinical estimation of residual tumor size is generally adequate, but those tumor cells in :

1. Lymphovascular space

2. Lymph node ˂ CT sensitive vs primary site

3. Parametrium

Discussion :

• Combination CT : Cisplatin & 5-FU → applied at The Norwegian Radiumhospital for treatment of recurrent cervical carcinoma, overall RR : 49%.

• Initial reports have demonstrated : short term results with surgical downstaging and improved resectability.

• Median overall and DFS was not reached, actuarial 5 year survival rate : 73% vs 67%.

• In our study : the number of pts. with LN (+) relatively low (bulky mass).

• The occurrence of recurrent disease in the pelvis indicates that neoadjuvant CT is able to extinguish distant metastasis.

Discussion :• To compare the efficacy and toxicity of NAC → HT

with those RT alone with bulky early-stage CC (phase III).

• DFS & OS : didn’t different significantly.

• Overall clinical response (OCR) after NAC : 86,2% (24,6% CR & 61,6% PR) ; pathologic CR : 3 pts (4,6%).

• Phase II : OCR → 24,2% CR & 60,6% PR; pathologic CR : 2 pts.

• Hence : once NAC applied → definite surgical approach to radically remove should be undertaken as the first priority.