Retrospective Analysis of Concomitant Cisplatin During Radiation in

Transcription

ORIGINAL ARTICLE
Retrospective Analysis of Concomitant Cisplatin During
Radiation in Patients Aged 55 Years or Older for
Treatment of Advanced Cervical Cancer
A Gynecologic Oncology Group Study
Charles Kunos, MD, PhD,* Chunqiao Tian, PhD,Þ Steven Waggoner, MD,þ Peter G. Rose, MD,§
and Rachelle Lanciano, MD||
Hypothesis: Patients with stages II to IVa cervical cancer aged 55 years or older were
compared with patients younger than 55 years who received weekly cisplatin during pelvic
radiation for differences in chemoradiation administration, toxicity, and outcome.
Methods: Retrospective review included patients enrolled on Gynecologic Oncology
Group trial Nos. 120 and 165 (n = 335) who received weekly cisplatin (40 mg/m2) during
pelvic irradiation (40.8Y50.1 Gy) followed by intracavitary brachytherapy (30Y40 Gy).
Results: For all 335 patients, 53% completed 6 cycles of chemotherapy during radiation
with no observed difference in frequency among patients younger than 55 years or 55 years
or older (P = 0.616). Excess hematological but not genitourinary toxicity was seen in
patients 55 years or older. At 5 years, 56% of patients younger than 55 years were predicted
to be alive and disease-free compared with 55% of those aged 55 years or older (P = 0.629).
A 5-year survival was 60% in patients younger than 55 years as compared with 56% in
patients aged 55 years or older (P = 0.265).
Conclusions: Patients aged 55 years or older with locally advanced cervical cancer undergoing concurrent weekly cisplatin with pelvic radiation on cooperative group clinical
trials achieve similar progression-free and overall survivals as younger patients. Disparity
was not observed in the seriousness or frequency of treatment-related sequelae.
Key Words: Cervical cancer, Chemoradiation, Elderly
Received April 7, 2009, and in revised form May 19, 2009.
Accepted for publication June 16, 2009.
(Int J Gynecol Cancer 2009;19: 1258Y1263)
*Department of Radiation Oncology, Case Comprehensive Cancer Center
and University Hospitals of Cleveland Case Medical Center, Cleveland,
Ohio; †Gynecologic Oncology Group Statistical and Data Center, Roswell
Park Cancer Institute, Buffalo, NY; ‡Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Case Comprehensive Cancer
Center and University Hospitals of Cleveland Case Medical Center;
§Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Case Comprehensive Cancer Center and The Cleveland Clinic,
Cleveland, OH; and ||Department of Radiation Oncology, Delaware County
Memorial Hospital, Drexel Hill, PA.
Address correspondence and reprint requests to Charles Kunos, MD, PhD,
Department of Radiation Oncology, University Hospitals Case Medical
Center, 11100 Euclid Ave, LTR 6068, Cleveland, Ohio 44106. E-mail:
[email protected].
This study was supported in part by a grant (K12 CA076917) to C.K. from
the National Institutes of Health and the Case Comprehensive Cancer
Center and also by National Cancer Institute grants to the Gynecologic
Oncology Group Administrative Office (CA 27469) and the Gynecologic
Oncology Group Statistical Office (CA 37517).
The following member institutions participated in this study: University of
Alabama at Birmingham, Oregon Health Sciences University, Duke
University Medical Center, Abington Memorial Hospital, University of
Copyright * 2009 by IGCS and ESGO
ISSN: 1048-891X
DOI: 10.1111/IGC.0b013e3181b33ace
1258
Rochester Medical Center, Walter Reed Army Medical Center, Wayne
State University, University of Minnesota Medical School, Emory
University Clinic, University of Southern California at Los Angeles,
University of Mississippi Medical Center, Colorado
Gynecologic Oncology Group, PC, University of California at Los
Angeles, University of Washington, University of Pennsylvania
Cancer Center, University of Miami School of Medicine, Milton S.
Hershey Medical Center, Georgetown University Hospital,
University of Cincinnati, University of North Carolina School of
Medicine, University of Iowa Hospitals and Clinics, University of
Texas Southwestern Medical Center at Dallas, Indiana University
School of Medicine, Wake Forest University School of Medicine, Albany
Medical College, University of California Medical Center at Irvine,
Tufts-New England Medical Center, Rush-Presbyterian-St Luke’s
Medical Center, SUNY Downstate Medical Center, University of
Kentucky, Eastern Virginia Medical School, The Cleveland Clinic
Foundation, Johns Hopkins Oncology Center, State University of New
York at Stony Brook, Eastern Pennsylvania GYN/ONC Center, PC,
Cooper Hospital/University Medical Center, Columbus Cancer Council,
University of Massachusetts Medical School, Fox Chase Cancer Center,
Medical University of South Carolina, Women’s Cancer Center,
University of Oklahoma, University of Virginia Health Sciences Center,
University of Chicago, University of Arizona Health Science Center,
Tacoma General Hospital, Mayo Clinic, Case Western Reserve
University, Tampa Bay Cancer Consortium, and The New York
Hospital/Cornell Medical Center.
International Journal of Gynecological Cancer
& Volume 19, Number 7, October 2009
Copyright @ 2009 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
C
ervical carcinoma ranks second among malignancies in women
worldwide, accounting for nearly 190,000 deaths annually.1
Age at diagnosis for new cases of cervical carcinoma has been
observed to follow a bimodal distribution, with peak ages at 30 to
39 years and 60 to 69 years. Age at diagnosis has been identified
as a risk factor for cancer relapse and death after chemoradiation for
locally advanced stages II to IVa cervical cancer. A prior Gynecologic
Oncology Group (GOG) multivariate study of nonYcisplatincontaining chemoradiation trials showed that older patient age was
significantly associated with less frequent cervical cancer relapse
or cancer-related death,2 yet contemporary cisplatin-containing
chemoradiation trials no longer identify patient age influencing
risk of relapse or survival after adjusting for cofactors.3Y8 Nevertheless, population-based studies have shown an increased disparity in cervical cancer incidence and mortality among patients aged
55 years or older.1,9
The US Surveillance, Epidemiology, and End-Results (SEER)
cancer registries reported a 35% incidence of cervical cancer but
55% cervical cancerYrelated mortality for patients aged 55 years or
older (1998Y2002).10 Explanations for the disparity between cervical
cancer incidence and mortality are lacking. Perhaps, patient chemotherapy administration during radiation is not being realized as
recommended by cooperative group clinical trials.3Y8 An earlier
national Patterns of Care Study evaluating practice patterns between
1996 and 1999 showed that 25% of patients 60 years or older
underwent chemoradiation for cervical cancer as compared with
48% among patients aged 40 years or younger (P = 0.02).11 Between 1998 and 2002, SEER-Medicare data show increased chemoradiation administration among women aged 55 years or older;
however, only 43% aged 55 years or older received concurrent
chemoradiation.9
Whether patients aged 55 years or older derive benefit from
chemoradiation treatment of cervical cancer remains relatively
unknown. This is, in part, because of limited numbers of patients
aged 55 years or older enrolled in clinical chemoradiation studies of
advanced cervical cancer. Beliefs that patients aged 55 years or older
tolerate chemoradiation more poorly may also lead to a lack of
clinical outcome benefit for chemoradiation.12 In the case of concurrent radiosensitizing cisplatin, perceived and actual hematological, genitourinary, and gastrointestinal sequelae often lead to the
practice of withholding chemoradiation for treatment of cervical
cancer in older patients.13,14
The purpose of this retrospective study was to evaluate chemoradiation administration, toxicity, and outcome of patients with
cervical cancer aged 55 years or older as compared with patients
younger than 55 years treated on GOG protocol Nos. 120 and 165.
METHODS
Detailed methodology for clinical trial GOG Nos. 120 and
165 have been published previously.3,4 Briefly, patients had untreated stage IIB, III, or IVA invasive squamous, adenosquamous,
or adenocarcinoma of the cervix. To establish clinical stage,
patients must have undergone complete physical examination, pelvic examination, and chest radiograph. Surgical staging was mandatory for GOG No. 120 but optional for GOG No. 165, with 18%
of GOG No. 165 study patients undergoing surgical staging.3,4
Patients with disease outside the pelvis, those with surgically or
radiographically confirmed para-aortic node metastasis or those not
candidates for radiation, were ineligible. Institutional review board
approval among participating institutions was obtained for clinical
trial GOG protocol Nos. 120 and 165. Written informed consent
consistent with institutional, state, and federal regulations was
obtained before entry on the study and randomization.
Chemoradiation in Women
Aged 55 Years or Older
Chemotherapy
Gynecologic Oncology Group Nos. 120 (n = 176) and 165
(n = 159) included patients randomly assigned to weekly cisplatin
chemotherapy (40 mg/m2) for 4 hours before radiation therapy on
days 1, 8, 15, 22, 29, and 36. Cisplatin chemotherapy was discontinued for leukopenia (GOG 0120 G 2500 or GOG 0165 G 3000
per cubic millimeter) or thrombocytopenia (GOG 0120 G 50,000 or
GOG 0165 G 100,000 per cubic millimeter) and resumed after resolution. For subsequent cycles, cisplatin chemotherapy was discontinued for neurotoxicity grade 3 and higher or a creatinine level
of more than 2 mg/dL. Gynecologic Oncology Group Nos. 120
and 165 did not specify growth factor administration.
Radiation
For GOG No. 120, anterior-posterior and posterior-anterior
or 4-field box technique pelvic radiation was delivered in 1.7-Gy
fractions using 4-MV photons or higher to doses ranging from
40.8 Gy for patients with stage II to 51.0 Gy for patients with stage
III/IVA. In GOG No. 165, 4-field box pelvic radiation was delivered
in 1.8-Gy fractions using 4-MV photons or higher to a dose of
45.0 Gy. In general, the 4-field box techniques used an upper margin
of the L5 vertebra and a lower margin of the midportion of the
obturator foramen or the lowest extent of disease with a 3-cm margin
for anterior and posterior radiation fields. Laterally, the anterior and
posterior radiation fields extended 1.5 to 2 cm beyond the pelvic
brim. For right and left lateral radiation fields, the anterior border
was the pubic symphysis, and the posterior border was the space
between the S2 and S3 vertebrae. The superior and inferior margins
for lateral radiation fields were the same as the anterior and posterior
radiation fields.
Intracavitary lowYdose rate brachytherapy followed external
beam radiation 1 to 3 weeks later. One or 2 applications were allowed.
LowYdose rate brachytherapy doses were 40.0 Gy for patients with
stage II and 30.0 Gy for patients with stage III/IVA on GOG protocol
No. 120 and 40.0 Gy for all stages on GOG No. 165, prescribed to
radiation prescription point A. If intracavitary brachytherapy could
not be delivered, additional external beam radiation to a dose of
61.2 Gy was done. Interstitial brachytherapy was not allowed on GOG
No. 120 or 165, but highYdose rate brachytherapy was allowed on
GOG No. 165. For GOG No. 165, highYdose rate brachytherapy
consisted of 5 fractions of 6.0 Gy (total dose, 30.0 Gy) started the
fourth week of external beam radiation with at least 1 fraction per week.
In both studies, total irradiation time was to be less than 10 weeks.
Radiotherapy was withheld for grade 3 or 4 leukopenia and up to
1 week for gastrointestinal or genitourinary radiation-related toxicity.
Statistical Analysis
Age groups were dichotomized at 55 years owing to the
disparity of cervical cancer incidence and mortality apparent in
SEER cancer registries10 and then at 70 years owing to an apparent
decrease in odds of chemotherapy use during radiation among
patients with cervical cancer in the US SEER-Medicare cancer
registry between 1998 and 2003.9 Age was dichotomized to
facilitate comparison to 1998Y2003 US SEER-Medicare data that
reflect cancer health service delivery to a highly skewed population
of women aged 55 years or older.9 Several parameters of chemotherapy were evaluated in relation to age groups. Relative dose
(RD) was the ratio of actual to expected dose of cisplatin in standard
chemotherapy (40 mg/m2 6 cycles). Relative time (RT) was defined as the ratio of actual to expected duration of chemotherapy
(6 weeks). Relative dose intensity (RDI) was defined as the ratio of
RD to RT. A ratio lesser than 1.0 indicated patients received less
intensity of chemotherapy than planned. Treatment completion was
defined as completing 6 cycles of chemotherapy because this was
the proposed number of cycles in the 2 GOG studies. Treatment
* 2009 IGCS and ESGO
1259
Kunos et al
TABLE 1. Patient characteristics by age group
Characteristic
Race
White
Black
Other
GOG performance status
0
1 or 2
Stage
II
III/IV
Tumor grade
1
2
3 or not graded
Histologic diagnosis
Squamous
Others
Tumor size, cm
G5
Q5
Parametrial involvement
Unilateral
Bilateral
Pelvic node
Positive
Negative/not done
Protocol treatment
GOG 120
GOG 165
TABLE 2. Treatment parameters by age group
G55 yr
(n = 232), %
Q55 yr
(n = 103), %
56.5
25.4
18.1
66.0
19.4
14.6
0.083
71.6
28.5
65.1
35.0
0.233
62.9
37.1
60.2
39.8
0.634
9.1
59.1
31.9
5.8
60.2
34.0
0.597
87.9
12.1
85.4
14.6
0.529
48.7
51.3
66.0
34.0
0.003
56.9
43.1
61.2
38.8
0.465
16.4
83.6
6.8
93.2
0.018
53.5
46.6
50.5
49.5
P
Pearson W2 method used to compare the difference in proportion between
2 groups.
toxicities were graded as defined in previous clinical reports.3,4
Progression-free survival (PFS) was calculated from date of patient
enrollment to the date of progression or recurrence of disease, death,
or most recent follow-up visit. Overall survival (OS) was calculated
from the date of patient enrollment to the date of death or last
contact.
The mean RD, RT, and RDI between patients younger than
55 years and patients aged 55 years or older were compared using
Student t test. The number of treatment cycles, cause of treatment
incompletion, and toxicity were compared by Pearson W2 test. The
factors associated with treatment incompletion were identified
using a logistic regression model. The cumulative probability of
PFS or OS was estimated by Kaplan-Meier procedure, and the logrank test was used to compare the difference of the distribution
between the 2 groups. All statistical analyses were 2 tailed (> = 0.05)
and were performed using Statistical Analysis System software
(SAS version 9.1; SAS Inc, Cary, NC).
RESULTS
Of 335 patients included for this analysis, median age was 49
years (range, 20Y80 years). Two hundred thirty-two patients were
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Treatment
Parameter
RD*
Mean (SD)
Median
(25thY75th Pct)
RT‡
Mean (SD)
Median
(25thY75th Pct)
RDI§
Mean (SD)
Median
(25thY75th Pct)
No. treatment
cycles, %
0
1
2
3
4
5
6
G55 yr
(n = 232)
Q55 yr
(n = 103)
P
0.85 (0.17)
0.84 (0.20)
0.830†
0.87 (0.79Y0.99) 0.88 (0.81Y0.97)
1.00 (0.27)
1.09 (0.79)
0.251†
1.00 (0.83Y1.14) 1.00 (0.83Y1.24)
0.87 (0.15)
0.86 (0.18)
0.547†
0.92 (0.79Y0.99) 0.94 (0.75Y0.98)
0.0
0.9
0.0
6.5
8.6
30.6
53.5
1.0
1.9
1.9
1.9
11.7
31.1
50.5
0.616||
*Ratio of actual to expected dose of chemotherapy.
†Student t test use to compare the difference between 2 groups.
‡Ratio of actual to expected duration of chemotherapy.
§Relative dose/RT.
||Pearson W2 used to compare the proportion of completion (53.5% vs
50.5%).
younger than 55 years, and 103 patients were 55 years or older.
There were 13 elderly patients (Q70 years) included in this analysis.
There were no significant differences between the 2 age groups in
the distributions of race, GOG performance status, clinical stage,
tumor grade, tumor histologic diagnosis, or parametrial involvement. However, larger tumors (P = 0.003) or pelvic lymph nodes
TABLE 3. Treatment-related adverse effects by age group
Adverse Effect
Grade 3 or 4 (selected)
Leukopenia
Thrombocytopenia
Other hematological
Gastrointestinal
Genitourinary
Neurological
Cutaneous
Any grade 3 or 4
G55 Yr
(n = 232), %
Q55 Yr
(n = 103), %
22.0
2.2
12.1
18.1
6.5
1.7
2.6
47.8
32.0
1.0
21.4
19.4
1.9
1.0
50.5
2.90.656
P*
0.050
0.671
0.028
0.775
0.082
1.000
1.000
*Pearson W2 or Fisher exact method used to compare the difference in
proportion between 2 groups.
with metastasis (P = 0.018) were observed more commonly among
patients younger than 55 years (Table 1).
Overall, 53% of patients completed 6 cycles of chemotherapy
during radiation. The mean RD, RT, and RDI were 0.85, 1.03, and
0.87, respectively (Table 2). Patients younger than 55 years or 55
years or older were equally likely to finish 6 cycles of chemotherapy
during radiation (54% vs 51%; P = 0.616), without differences in
RD, RT, and RDI (Table 2). For the 13 elderly patients (Q70 years), 7
(54%) completed 6 cycles of chemotherapy during radiation.
In this study population, 49% of patients reported at least 1
grade 3 or 4 adverse effect without difference between age groups
younger than 55 years and 55 years or older. Although thrombocytopenia, genitourinary, and neurological and cutaneous toxicities
were rare, a higher proportion of patients aged 55 years or older
experienced leukopenia (32% vs 22%; P = 0.050) and other
hematological (21% vs 12%; P = 0.028) toxicities during chemoradiation (Table 3). Nine (69%) of 13 patients aged 70 years or older
experienced at least 1 grade 3 or 4 adverse effect.
After controlling for other clinical factors and treatment
protocol (Table 4), patients aged 55 years or older were no more
TABLE 4. Factors associated with treatment incompletion
Characteristic
Incompletion, %
OR (95% CI)
46.6
49.5
Referent
1.16 (0.71Y1.89)
43.3
60.8
45.2
Referent
2.13 (1.22Y3.74)
1.09 (0.61Y1.96)
45.9
51.0
Referent
1.27 (0.76Y2.11)
50.5
42.5
Referent
0.70 (0.43Y1.13)
Age group, yr
G55
Q55
Race
White
African American
Other
Performance status
0
1 or 2
Stage
II
III/IV
Histologic diagnosis
Squamous
Others
Tumor grade
1
2
3
Tumor size, cm
e5
95
Parametrial
involvement
Unilateral
Bilateral
Pelvic node
Positive
Negative/not done
P*
0.552
0.029
0.361
0.146
Referent
0.70 (0.36Y1.39)
44.4
45.7
51.4
Referent
1.13 (0.49Y2.61)
1.53 (0.64Y3.68)
49.2
45.5
Referent
0.85 (0.53Y1.34)
FIGURE 1. Kaplan-Meier estimate of PFS for patients younger
than 50 years and patients aged 50 years or older.
likely to stop cisplatin chemotherapy during radiation as compared
with patients younger than 55 years (odds ratio [OR], 1.16; 95%
confidence interval [CI], 0.71Y1.89; P = 0.552). The only factor
potentially affecting treatment completion was race, as AfricanAmerican patients had a greater frequency of not completing prescribed protocol therapy than white patients (OR, 2.13; 95% CI,
1.22Y3.74; P = 0.029). Reasons describing why a patient did not
complete prescribed protocol therapy were not encoded for these
clinical trials.
At the time of this report, 169 patients showed disease progression, including 157 deaths. Median follow-up duration for
patients still alive was 94 months, with a maximum follow-up of
169 months (25%Y75% quartile, 78Y123 months). At 5 years, 56%
of patients younger than 55 years were predicted to be alive and
disease-free compared with 55% of those aged 55 years or older
(Fig. 1). The distribution of PFS was essentially the same (log-rank
test: P = 0.629). There was also no significant difference in OS
between the 2 groups (log-rank test: P = 0.265), with a 5-year
survival of 60% in patients younger than 55 years compared with
56% in patients aged 55 years or older (Fig. 2).
DISCUSSION
0.310
48.6
39.5
This report confirmed that in the cooperative group, clinical
trial setting, chemoradiation administration, toxicity, and outcome of
patients with cervical cancer aged 55 years or older are similar to
0.406
0.481
0.580
49.2
45.0
Referent
0.87 (0.54Y1.42)
48.3
42.2
Referent
0.81 (0.41Y1.57)
0.524
*Odds ratio estimated by Logistic regression model, adjusted for
covariates and protocol.
FIGURE 2. Kaplan-Meier estimate of OS for patients younger
than 50 years and patients aged 50 years or older.
1261
Kunos et al
patients of younger age. Given that chemoradiation use for locally
advanced cervical cancer has risen steadily because of publication of
5 chemoradiation clinical trials, patients aged 55 years or older were
expected to have similar risks of cancer-related relapse or death as
compared with patients younger than 55 years.4Y8 For given tumor
and demographic factors for patients enrolled in GOG Nos. 120 and
165, patients aged 55 years or older were just as likely to complete
all recommended chemotherapy treatments during radiation as
patients of younger age.
Retrospective analyses of population-based cancer registries
have not encoded detailed chemotherapy administration records.
Unlike population-based cancer registry studies, this retrospective
analysis of 2 cooperative group clinical trials offered reliable
abstraction of the exact regimen of chemotherapy administration,
patient-specific chemotherapy dosage, and adverse effects of
treatment. In this study, ratios of actual delivered chemotherapy
dose to expected dose, actual to expected time of chemotherapy
delivery, and RD to RT were determined for GOG protocols Nos.
120 and 165. The observed RD, RT, and RDI were similar among
treated patients regardless of age (Table 2), even among the limited
number of patients aged 70 years or older. Certainly, this finding is
open to interpretive criticism. Not only patients participating in
clinical trials are often highly motivated to complete protocol
prescription therapy, but also physicians are highly motivated to
have their patients complete all protocol prescription therapy. For
instance, in the 1998Y2002 SEER-Medicare population cervical
cancer registry, only 47% of patients aged 55 years or older treated
for locally advanced cervical cancer with radiation received at least 5
cycles of concomitant chemotherapy.9 A significant decreased odds
of radiation and chemotherapy administration in patients aged
71 years or older was also observed.9 By comparison, 84% of
patients younger than 55 years and 82% of patients aged 55 years or
older completed at least 5 cycles of chemotherapy in GOG protocol
Nos. 120 and 165. Perhaps, patient and physician motivations and
possibly overall ancillary treatment support provided by controlled
cooperative group clinical trials accounts for the disparity in
chemotherapy use during radiation administration among SEERMedicare and GOG patient populations.
In previous retrospective analyses, it has been noted that
physician bias, attributed to elderly patient moderate-to-severe
medical comorbidity, adversely impacts allocation of primary and
adjuvant therapies for patients with cancer.12,15Y17 In this report,
there was not an overall excess incidence of treatment-related toxicity in patients aged 55 years as compared with younger patients
(Table 3). For patients aged 55 years or older, the proportion of
those alive and free of disease was similar to younger patients, at
a cost of an increased incidence of manageable grade 3 and higher
hematological toxicity. Growth factors were not used in either
GOG protocol Nos. 120 or 165 and, perhaps, with further study in
the 55-year or older patient population, could lessen hematological
toxicity. Genitourinary toxicity was not higher in patients aged
55 years or older despite the more probable increased incidence of
impaired renal function in these patients.
While treatment-related toxicity was not a barrier to finishing
chemotherapy, there was a disparity in the proportion of AfricanAmerican patients not completing prescribed chemotherapy during
radiation. Among African-American patients, there was not an
identifiable treatment-related factor or toxicity associated with not
completing prescribed therapy. For GOG Nos. 120 and 165,
compelling evidence explaining the observed disparity of treatment
completion was not identified in multivariate analyses.14 Radiation
dose and brachytherapy technique were different in GOG Nos. 120
and 165, but too few patients (21 enrolled on GOG 165 [6%] of the
335 total studied here) underwent highYdose rate brachytherapy to
comment.3 Perhaps, one explanation could be found among
1262
differences in poverty and education levels, as these factors have
been associated with lower likelihoods of completing prescribed
therapy, which translates into poorer survival.18Y20 In population
studies using SEER cancer incidence data, disparity between 5-year
survival rates were 7% between low and high poverty and 7%
between low and high education census tracts.18 Among patients
studied for this analysis, reliable proxy indicators of socioeconomic
and educational statuses were not readily coded for analysis and,
thus, cannot be commented upon as contributing factors to incomplete protocol treatment administration.
With a median follow-up of 94 months among survivors,
patients aged 55 years or older were not more likely to relapse or die
of cervical cancer as compared with patients younger than 55 years
when radiosensitizing doses of cisplatin chemotherapy were administered. Within the cohorts aged 55 years or older and younger
than 55 years of GOG Nos. 120 and 165, subpopulations do fare
better, as a nonlinear association between age and survival has
been observed with patients aged 51 to 60 years having a better
prognosis than those patients aged 40 years or younger.14 As such,
substantial gains in PFS and OS observed for patients in these
cohorts perhaps may only be applicable when cisplatin chemotherapy is used. Concurrent weekly cisplatin with pelvic radiation
significantly improves long-term PFS and OS as compared with
radiation alone for patients with cervical cancer.4Y6 Whether other
radiosensitizing chemotherapeutic agents achieve these gains
remains unanswered. For patients aged 55 years or older who do
not receive cisplatin chemotherapy owing to medical comorbidity or
lack of administrative ability, other agents that can be safely and
reliably given during radiation should be studied. The GOG and
other large cooperative groups continue to refine the optimal
regimen for chemoradiation in the treatment of patients with locally
advanced cervical cancer.
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