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’s
and 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.