Cervical Carcinoma

Chris DeSimone, M.D.

Assistant Professor
Division of Gynecologic Oncology
Outline
 Cervical Carcinoma
 Epidemiology

 Clinical symptoms

 Risk factors

 Staging

 Cell types

 Prognostic factors

 Treatment
Cervical Cancer
 2nd most common cancer among women
world wide
 Estimated 493,000 new cases
 293,000 deaths annually worldwide
 7th most common cancer among women in
the United States
 Estimated 10,000 new cases each year
 3700 deaths annually from cervical cancer

Parkin et al. Int J Cancer, 2005.

Who Develops Cervical
Cancer?
 50% of women diagnosed with cervical cancer have
not had a Pap test in 5 years
 25% of all cervical cancers are diagnosed in women
older than 65
 In women older than 65, it is estimated that over
50% have not had a Pap test in the past 10 years

 Bottom Line – the majority of women with cervical

cancer fail to get annual Pap tests
Symptoms
 Early stages
 Vaginal bleeding
 Post coital spotting
 Foul smelling, yellowish discharge
 Late stages
 Back pain
 Lethargy
 Nausea/vomiting
 Most symptoms attributable to renal failure from ureteral
obstruction
Classic Risk Factors for Cervical
Cancer
 Early first age of sexual contact
 Multiple sexual partners
 Smoking
 Multiple sexually transmitted diseases
 Immunocompromised
 Lower socio-economic class
 Family history is not a risk factor
Main Risk Factors for Cervical
Cancer
 Human papillomavirus (HPV) is the cause of
cervical cancer
 Estimated that 80% of men and women will
have been exposed to the virus by the age of
50
 Smoking is an important cofactor for
malignant transformation
Staging of Cervical Cancer
 Clinically staged (at least partially)
 Stage I is confined to the cervix
 Ia1
 Stromal invasion < 3 mm and lateral spread < 7 mm

 Ia2
 Stromal invasion 3-5 mm and lateral spread < 7 mm lateral
spread
 Ib1
 Clinically visible lesion ≤ 4 cm

 Ib2
 Clinically visible lesion > 4cm in greatest dimension
Staging of Cervical Cancer
 Stage IIa
 Upper 2/3 of vagina
 Stage IIb
 Parametrial involvement
 Stage IIIa
 Lower 1/3 of vagina
 Stage IIIb
 Pelvic sidewall or hydronephrosis
 Stage IVa
 Rectal or bladder mucosa
 Stage IVb
 Distant disease
Cervical Anatomy
Cell Types
 Squamous (80%)
 Squamous cell
 Large cell keratinizing
 Large cell non-keratinizing
 Grade 2 most common grade
 Adenocarcinoma (20%)
 Incidence is increasing ~30% (70’s to 90’s)
 Adenocarcinoma
 Mucinous (rare)
 Endometrioid
 Clear Cell (DES exposure)
 Adenosquamous
 malignant glandular and squamous cell types
 Poor prognosis
Cell Types
 Glassy Cell Carcinoma
 Poorly differentiated adenosquamous carcinoma with
eosinophilic cytoplasm
 Poor prognosis
 Adenoid Cystic Carcinoma
 Cribriform gland pattern
 Aggressive and poor prognosis
 S100 immunohistochemistry
 Adenoid Basal Carcinoma
 Indolent and excellent prognosis
 Neuroendocrine tumors
 Carcinoid
 Small-cell carcinoma
 Strong association with HPV 18
 Chemosensitive but recurrences likely
 Surgical treatment best therapy
 Chromogranin and neuronspecific enolase immunohistochemistry
Survival Rates
 Ia 95%
 Ib 80%
 II 63%
 III 36%
 IV 15%

 Benedet J. Annual report on the treatment of GYN CA. J Epidemiol Biostat, 2001.
Prognostic Factors
 Age
 Women < 35 have a poorer prognosis?
 No conclusive data to support this concept
 Race
 African –American women are more likely to have
numerous risk factors, advanced stage and less likely to
undergo therapy
 Anemia
 Grogan et al. Cancer; 1999.
 475 patients evaluated
 Presenting hemoglobin ≥ 12 g/L had a better prognosis
 Significant on univariate analysis ONLY
Prognostic Factors
 Tumor Invasion/Size
 Delgado et al. Gynecol Oncol; 1990. GOG 49.
 Patients with minimal stromal invasion had better 3 year
survival rates following radical hysterectomy
 < 10 mm: 86-94%
 11 to 20 mm: 71 to 75%
 > 21 mm: 60%

 van Nagell et al. Cancer; 1979.

 Recurrence rate for Ib cervical cancers: RAH vs. XRT
 Tumor <2 cm: 5% recurrence for RAH or XRT
 Tumor 2-5 cm: 24% recurrence with RAH, 11% with XRT
Prognostic Factors
 Stage
 Stehman et al. Cancer; 1991.
 Confirmed that tumor burden is a poor prognostic factor
 Clinical staging limits thorough evaluation of tumor burden
such as tumor volume, nodal status etc; therefore stage
not the best indicator of a patient’s prognosis

 Lymph Vascular Space Invasion

 Delgado et al. Gynecol Oncol; 1990. GOG 49.
 Disease free survival 77% with LVSI vs. 89% without LVSI
Prognostic Factors
 Nodal Status
 The MOST significant negative prognostic factor
 Tinga et al. Gynecol Oncol; 1990 and Delgado et
al. Gynecol Oncol; 1990. GOG 49.
 Higher 5 year survival rates among surgically
treated patients with negative LN’s (90%), positive
pelvic LN’s (50-60%) and positive para-aortic LN’s
(20-45%)
 Reported 87% survival rate for 1 involved LN vs.
53% for 2 or more involved LN’s (p<0.02)
Parametrial, Pelvic and Para-
aortic Lymph Node
Involvement per Stage
Stage Parametrial Pelvic Para-aortic

Ia2 - 5% 1%
Ib 11% 15% 5%
IIa - 22% 15%
IIb 22% 35% 20%
III - 45% 35%

Hoskin's. 4th ED. 745.

Treatment for Stage I
 Surgery is reserved for early staged cervical
cancer
 Stage Ia1
 Cervical cone
 Hysterectomy
 Stage Ia2, Ib 1 and some Ib2 or IIa
 Radical hysterectomy (abdominal, vaginal or
laparoscopic)
 Fertility-sparing: radical trachelectomy
Radical Hair
Radical Hysterectomy
 Objective is to remove the cervical cancer,
uterus and tissue adjacent to the uterus:
 Parametrial tissue
 Complete pelvic lymphadenectomy (internal,
external, common iliac nodes and obturator
nodes)
 Upper 2 cm of the vagina
 Higher morbidity than a simple hysterectomy
Types of Radical
Hysterectomies
Extrafascial Type I Modified Radical Type II Radical Type III

Cervical Fascia Completely removed Completely removed Completely removed

Vaginal Cuff Small rim removed Proximal 1-2 cm Upper ⅓ to ½ removed

Bladder Partially mobilized Partially mobilized Mobilized

Rectum Partially mobilized Partially mobilized Mobilized

Ureters Not mobilized Unrooted in ureteral tunnel Complete dissection to bladder

entry
Cardinal Ligament Resected medial to ureters Resected at level of ureter Resected at pelvic sidewall

Uterosacral Resected at level of cervix Partially resected Resection at post-pelvic

Ligaments insertion
Uterus Removed Removed Removed

Cervix Completely removed Completely removed Completely removed

Extended Radical - - Above plus, resection of

Hysterectomy Type superior vesical artery and
IV more vagina
Type V - - Above plus, resection of ureter
and bladder
Radical Hysterectomy
Anatomy
Radical Hysterectomy
Anatomy
Radical Hysterectomy
Anatomy
Complications of Radical
Hysterectomy
 Estimated that 10% of patients will have
some form of bladder dysfunction or injury
 Ueland et al. Gynecol Oncol, 2005.
 Evaluated 290 RAH’s from 1965-2002
 Since 1985, incidence of ureteral injury <2%,
bladder injury <1% and fistulas <1%
 These injuries were more common when EBL
>1000 ml (p<0.01)
 Pulmonary embolis
 Transfusion
Survival Rate from Radical
Hysterectomy
 Related to size of the tumor
 Generally 90% 5-year survival rate
 Ueland et al. Gynecol Oncol, 2005.
 All size Ib1 tumors
 98% 2-year, 96% 5-year, 94% 10-year
 Gadduci et al. Anticancer Res, 1995.
 ≤4 cm, 92% 5-year
 >4 cm, 56% 5-year (p=0.001)
 Hopkins et al. Am J Obstet Gynecol, 1991.
 ≤3 cm, 91% 5-year
 >3 cm, 76% 5-year (p=0.007)
Positive Lymph Nodes
Following RAH
 Positive lymph nodes equate to poor
prognosis
 Ib1 survival with RAH and (-) LN’s 80-90%
 Ib1 survival with RAH and (+) LN’s 50-60%
 Several studies document decreased local
recurrence with XRT; BUT no improvement in
overall survival

 What about Chemo/XRT?

Delgado et al. Gynecol Oncol. 1990.
Positive Lymph Nodes
Following RAH
 Peters WA et al. J Clin Oncol, 2000. GOG 109.
 Randomized study for Ia2-IIa cervical carcinomas
treated by RAH with positive lymph nodes
 Treatment group consisted of XRT versus
Chemo/XRT
 XRT: 4900 cGy. No brachytherapy
 Chemo: q 21 days
 Cisplatin 70 mg/m2 D1
 5-FU 1000mg/m2 D2-5
Positive Lymph Nodes
Following RAH
 Majority of women stage Ib cervical carcinomas and
majority had positive pelvic lymph nodes
 Median follow up 42 months
 4 year survival:
 Chemo/XRT 81%
 XRT 71% HR 1.96 (p=0.007)
 Toxicity:
 Chemo/XRT grade 4 toxicity (n=27) [Neutropenia 11]
 XRT grade 4 toxicity (n=4)
Radical Fashion
High Risk Groups s/p RAH
with (-) LN’s
 Risk factors significant for recurrence
 Depth of invasion
 Size of tumor
 LVSI

 Estimated 25% of Ib tumors with negative

pelvic lymph nodes have these factors
 GOG 49- Delgado et al. Gynecol Oncol,
1990.
High Risk Groups s/p RAH
with (-) LN’s
 Sedlis et al. Gynecol Oncol, 1998. GOG 92
 Randomized study for Ia2-Ib2 cervical carcinomas
treated by RAH with negative lymph nodes AND:
 > ⅓ stromal invasion (>15 mm)
 LVSI (positive)
 Large clinical tumor (>4 cm)

 Treatment group consisted of XRT versus no further

therapy (NFT)
 XRT: 4600 to 5040 cGy. No brachytherapy
High Risk Groups s/p RAH
with (-) LN’s

 21 patients (15%) recurred with XRT versus 39 patients

(28%) with no further therapy
 Majority of recurrences local 18/21 XRT vs. 27/39 NFT
 47% reduction in risk of recurrence: RR 0.53, p=0.008
 Recurrence free rate at 2 years 88% XRT vs. 79% NFT
 11 patients with Grade 3-4 toxicity with XRT vs. 3 with
NFT (majority GI and/or GU complications)
High Risk Groups s/p RAH
with (-) LN’s
 Summary
 Deep stromal invasion > 15 mm
 LVSI
 Tumor > 4 cm
 Negative LN’s

 Tailor therapy per patient for XRT ± Cisplatin

Radical Hippies

Arrow
points to
the hippy
 Neoadjuvant Chemotherapy and
RAH for Bulky Cervical Disease
Reference FIGO Stage Chemo regimen NACT+S Control Median Overall
follow up Survival
(5 year)

Chang et al. J Clin Ib-IIa Cisplatin 50mg/m2 D1 68 52 39 months 70% vs. 62%,
Oncol, 2000. Vincristine 1mg/m2 D1 p=0.77
Bleomycin 25 mg/m2 D1-3
q 10 days for 3 cycles
Benedetti-Panici et al. J Ib2-III Cisplatin 80 mg/m2 D1-2 152 144 79 months 56% vs. 44%,
Clin Oncol, 2002. Bleomycin 15 mg/m2 D1,8 p=0.01
q 21 days for 2 cycles

Cisplatin 50 mg/m2 D1
Vincristine 1 mg/m2 D1
Bleomycin 30 mg D1
6 weekly cycles

Cisplatin 43 mg/m2
Ifosfamide 3.5mg/m2 on
cycles 1,4,7
7 weekly cycles

Cisplatin 40 mg/m2 for 6

cycles
Neoadjuvant Chemotherapy and
RAH for Bulky Cervical Disease
 Too few studies to change standard of care
 OK to tailor treatment
 Awaiting more studies to determine if this
option is feasible
Radical Smokers
Radical Laparoscopic
Hysterectomy
 Ramirez et al. Gynecol Oncol, 2006.
 Case series of 20 patients who underwent total
laparoscopic radical hysterectomy
 18 cervical carcinomas (5 Ia2 and 13 Ib1)
 Median age 41 (range, 25-76 years)
 Median weight 70 kg (range, 49-112 kg)
 Median blood loss 200 ml (range, 25-700 ml)
 Median OR time 333 minutes (range, 275-442 minutes)
 Median hospital stay 1 day (range, 1-5 days)
 5 patients (25%) had complications (P.E., cystotomy,
pneumomediastinum, vaginal evisceration and lymphocyst)
 Median follow up 8 months all patients NED
Radical Laparoscopic
Hysterectomy
 Spirtos et al. Am J Obstet Gynecol, 2002.
 Evaluated 78 patients with total laparoscopic radical
hysterectomy
 78 cervical carcinomas (26 Ia2 and 52 Ib1)
 Median age 41 (range, 26-62 years)
 5 patients converted to laparotomy, one for a cystotomy
 Median blood loss 250 ml (range, 50-700 ml)
 Median OR time 205 minutes (range, 150-430 minutes)
 Median hospital stay 2.9 day (range, 1-7 days)
Radical Laparoscopic
Hysterectomy
 Results
 9 patients (11%) had positive lymph nodes
 10 patients (13%) had complications (cystotomy ×3, UV fistula,
DVT, urosepsis, vaginal cuff abscess, abdominal wall hematoma
and lymphocyst ×2)
 Mean follow up 68 months
 8 patients (10%) have had a recurrence
 3 pelvic sidewall
 1 external iliac artery distal to the deep C.I.
 1 vaginal apex
 1 liver
 1 pulmonary
 1 suprarenal LN
 5 patients have died, 93% 5 year survival rate
 3 recurrent disease
 1 CAD
 1 sepsis and bowel obstruction, 1 months out from surgery
Radical Laparoscopic
Hysterectomy
 Steed et al. Gynecol Oncol, 2004.
 Compared 71 cases of laparoscopic assisted
radical vaginal hysterectomy (LAVRH) to 205
cases of RAH.
 Retrospective analysis
 No differences in tumor size, histology,
grade, depth of invasion, lymph node
metastases or surgical margins
 No conversions to laparotomy
Radical Laparoscopic
Hysterectomy
 Results (LAVRH vs. RAH)
 EBL: 300 ml vs. 500 ml (p<0.001)
 OR time: 3.5 hrs vs. 2.5 hrs (p<0.001)
 Intraoperative complications 13% vs. 4% (p<0.03)
 LAVRH: cystotomy ×7, ureteral injury and bowel
perforation
 Hospital stay: 1 day vs. 5 days (p<0.001)
 Median follow up: 17 months vs. 21 months
 Recurrences: 4 vs. 13 patients (NS)
 2 year survival: 94% vs. 94% (NS)
Radical Laparoscopic
Hysterectomy Summary
 Total laparoscopic and laparoscopic assisted radical
hysterectomy can be safely employed to treat early
stage cervical carcinoma
 Not gold standard therapy
 Longer OR time and more complications with
laparoscopy
 Benefit: shorter hospital stay and blood loss
 Survival and recurrence rates are comparable
 Need a phase III trial between RAH vs. total
laparoscopic RAH
Radical Comics
Radical Trachelectomy
 Conservative (relatively) therapy designed to
preserve the uterus for child bearing while
removing the cervical carcinoma
 Preserves uterine arteries
 Cervix and parametrium are resected along
with pelvic lymph nodes
 Ideally suited for Ia 2 and small Ib1 tumors
Radical Trachelectomy
Radical Trachelectomy
 Shepherd et al. BJOG, 2006.
 Reported on a series of 123 vaginal radical
tracheletomies
 2 stage Ia2 and 121 stage Ib1
 Mean age 30 (range, 21-45 years)
 11 women (8%) underwent definitive RAH (2) or
Chemo/XRT (9) for positive lymph nodes and close
margins
 6 intraoperative complications: cystotomy and pelvic
hemorrhage ×4 and uterine perforation
 Mean follow up 45 months
Radical Trachelectomy
 Results
 3/112 recurrences (3%) for vaginal radical
trachelectomy (2 DOD)
 63 women attempted pregnancy
 55 pregnancies in 26 women
 28 live births in 19 women
 5-year pregnancy rate is 53%
 All but 2 women delivered by classical C/S
 7/28 infants were preterm < 32 weeks gestation
Radical Trachelectomy
Summary
 Acceptable method for treating early cervical
carcinoma
 Moderate success rate for pregnancy
 Few centers perform this surgery
 Counsel patient she will likely have preterm
labor and a C/S
Treatment for Stage II-IVa
 Stages II-IVb receive radiation (XRT) and
chemotherapy
 XRT given in two phases
 1st 5-6 weeks of external beam radiation
 Total dose 45 to 50 Gy
 Or 180 to 200 cGy each day
 Cisplatin 40 mg/m2 Q week

 2nd Brachytherapy
 HDR or LDR
 Positions a radioactive implant adjacent to the carcinoma
Radical Radiation
XRT
 Field size
 16 by 16 cm field
 Superior border- L4-L5 interspace
 Lateral border- 2 cm lateral to bony pelvis
 Inferior border- inferior border of the obturator
foramen
 Field covers external and internal iliac LN groups
XRT
 Brachytherapy
 Low dose rate (LDR)- 40-200 cGy/hour
 High dose rate (HDR)- >1200 cGy/hour
 Generally, higher dose rates increase late
reactions: fistulas
 Benefit- less acute reactions and better
compliance
 LDR 36 hours vs. HDR 4 hours
XRT
 Brachytherapy
 HDR delivers 5 fractions of 6 Gy or 30 Gy total
dose
 No significant difference between survival rate of
LDR and HDR
 No randomized trials in the US have compared
HDR to LDR
 Many studies show a trend (but NS) for better
survival rates with LDR
 Chemoradiation
Study Stage N Treatment Follow up Median 3 Significance
year
Survival
(%)
GOG #85 IIb-IVb 177 EB+BT+ Cisplatin 50 mg/m 2 (D1, 29) 8.7 years 67 OS p=0.018, RR 0.74
Whitney et al -PALN 5- FU 1000mg/m2 (D2-5 & D30-33)

199 EB+BT+ Hydroxyurea 80mg/kg 2× week 57

GOG #120 IIb-IVb 176 EB+BT+ Cisplatin 40mg/m 2 week 35 months 65 OS p=0.004, RR 0.61
Rose et al -PALN
173 EB+BT+ Cisplatin 50 mg/m 2 (D1, 22) 65 OS p=0.002, RR 0.58
5-FU 1000mg/m2 (D2-5 & D23-26)
Hydroxyurea 2gm/m 2 2× week

177 EB+BT+ Hydroxyurea 3gm/m 2 2× week 47

RTOG #9001 Ib-IVa 195 EB+BT+ Cisplatin 75 mg/m 2 (D1) Q 3 weeks ×2 43 months 75 OS p=0.004, RR 0.59
Morris et al 5-FU 1000 mg/m2 (D2-5)

193 EB+BT 63
GOG #123 Ib-IIa 183 EB+BT+ Cisplatin 40 mg/m 2 week + hysterectomy 36 months 83 OS p=0.008, RR 0.54
Keys et al
186 EB+BT+ hysterectomy 74

GOG #109 Ia2-IIa 127 EB+ Cisplatin 70 mg/m 2 (D1) Q 3 weeks ×2 42 months 87 OS p=0.01, RR 0.49
Peters et al s/p 5-FU 1000 mg/m2 (D2-5)
RAH
116 EB 77
Advanced Disease (Stage IVb)
 Current trend is chemotherapy
 Advanced (stage IVb) receive palliative XRT and
chemotherapy
 Chemotherapy of choice is Cisplatin- response rate
of ~ 30%
 GOG # 204 treats stage IV cervical cancer with
combinations of Cisplatin and:
 Vinerolbine
 Gemzar
 Topotecan
 Taxol
Recurrent Disease
 Possible treatments
 XRT
 Surgery
 Chemotherapy
Recurrent Disease (XRT)
 Local recurrence to the vagina and pelvis can
be salvaged with XRT
 Tissues do not have the same tolerance to
XRT, therefore severe late effects observed
 Best employed for patients with a long
disease-free interval
 Mainstay: interstitial or intracavitary XRT
 Small number of patients reported in the
literature
Recurrent Disease (XRT)
 Puthawala et al. Cancer, 1982.
 Interstitial implants
 7/10 patients experienced tumor control
 30% had mild proctitis, cystitis
 10% severe complication rate (RV, VV, EV fistulas)
 Randall et al. Gynecol Oncol, 1993.
 Interstitial implants (30-50 Gy) and LDR implants
 13 patients treated, median follow up 59 months
 69% CR and 46% NED after 2 years
 Squamous histology, small tumor volume and proximal
vaginal recurrences did better
 1 patient had a RV fistula
Recurrent Disease (XRT)
 Wang et al. Am J Obstet Gynecol, 1999.
 73 patients
 20-40 Gy given using LDR and HDR
 40% 5 year survival rate
 Favorable prognosis for tumors <4 cm and
proximal vaginal involvement
 12% fistula rate
Recurrent Disease (Surgery)
 Exenteration traditionally used for central
recurrences
 Modern Chemo/XRT leads to few isolated
central recurrences
 Exenteration includes removal of the uterus,
cervix, tubes, ovaries, and parametria PLUS:
 Bladder (Anterior exenteration)
 Rectum/Sigmoid (Posterior exenteration)
 Both (Complete exenteration)
Recurrent Disease (Surgery)
 Pre operative assessment
 Clinical exam: fixed pelvic lesion, weight loss,
hydronephrosis, leg edema and hip pain. These findings
are not suitable for the exenterative surgery
 CT scan ± PET scan for pelvic and para-aortic
lymphadenopathy, ascites and pelvic masses
 Shingleton et al. Obstet Gynecol, 1989.
 Defined risk groups for exenteration candidates
 Time from initial therapy to recurrence
 Size of recurrence
 Preoperative pelvic sidewall fixation
 Patients with recurrence <1 year, tumors > 3 cm and pelvic
sidewall fixation all died of complications or carcinoma
within 18 months of exenteration
Recurrent Disease (Surgery)
Exenteration facts
 Morbidity rate 15%
 Most common Author Patients (N) 5-year survival
rate (%)
complication is
transfusion Bricker 1960 150 25

 Enteric fistulas next most Symmonds 198 33

1975
likely complication
Rutledge 1977 296 34
 Mortality 5-8%
Morley 1989 100 61
 Permanent colostomy,
ileal conduit or continent Lawhead 1989 65 23
vesicostomy and a
TRAM flap/ gracilis flap
needed
Recurrent Disease
(Chemotherapy)
 Cisplatin is the drug of choice for advanced or
distally recurrent cervical cancer
 Dose established at 50 mg/m2
 Bonomi et al. J Clin Oncol, 1985.
 Compared Cisplatin at 100 mg/m2 to 50 mg/m2
 No difference in response rate, progression free
interval and survival
 Studies today focusing on using Cisplatin with
another agent
Recurrent Disease
(Chemotherapy)
 Omura et al. J Clin Oncol, 1997. GOG 110.
 Compared:
 Cisplatin 50 mg/m2 vs. (N=140)
 Cisplatin 50 mg/m2 and Ifosfamide 5 g/m2 (24 hr
infusion) every 21 days (N=151)
 Stage IVb, persistent or recurrent cervical
carcinomas
Recurrent Disease
(Chemotherapy)
 Results
 C/Ifos had a higher response rate (31% vs. 18%,
p=0.004)
 C/Ifos had a longer progression-free survival (4.6
vs. 3.2 months, p=0.003)
 No difference in overall survival
 C/Ifos had greater neutropenia, renal toxicity,
peripheral neuropathy and CNS toxicity
Recurrent Disease
(Chemotherapy)
 Moore et al. J Clin Oncol, 2004. GOG 169.
 Compared:
 Cisplatin 50 mg/m2 vs. (N=134)
 Cisplatin 50 mg/m2 and Taxol 135 mg/m2 every
21 days (N=130)
 Stage IVb, persistent or recurrent cervical
carcinomas
Recurrent Disease
(Chemotherapy)
 Results
 C/Taxol had a higher response rate (36% vs.
19%, p=0.002)
 C/Taxol had a longer progression-free survival
(4.8 vs. 2.4 months, p<0.001)
 No difference in overall survival
 C/Taxol had greater Grade 3 and 4 neutropenia
and anemia
Recurrent Disease
(Chemotherapy)
 Long et al. J Clin Oncol, 2005. GOG 179.
 Compared:
 Cisplatin 50 mg/m2 vs. (N=146)
 Cisplatin 50 mg/m2 and Topotecan 0.75 mg/m2
D1-3 every 21 days (N=147)
 Stage IVb, persistent or recurrent cervical
carcinomas
Recurrent Disease
(Chemotherapy)
 Results
 C/Topo had a higher response rate (27% vs.
13%, p=0.004)
 C/Topo had a longer progression-free survival
(4.6 vs. 2.9 months, p=0.014)
 C/Topo had a greater overall survival (9.4 vs. 6.5
months, p=0.017)
 C/Topo had greater Grade 3 and 4 hematologic
toxicity (70% vs. 1.4 %)