Decreased dose density of standard chemotherapy
does not compromise survival for ovarian
A. MOLCKOVSKY*, S.M. VIJAY*, W.M. HOPMAN*, P. BRYSONy, J.F. JEFFREYy & J.J. BIAGI*
*Department of Oncology and yDepartment of Obstetrics and Gynecology, Queen’s University, Kingston,
standard chemotherapy does not compromise survival for ovarian cancer patients. Int J Gynecol Cancer
Molckovsky A, Vijay SM, Hopman WM, Bryson P, Jeffrey JF, Biagi JJ. Decreased dose density of
For women diagnosed with ovarian cancer, the standard practice of surgery followed by adjuvant
platinum–taxane combination chemotherapy, with cycles administered every 3 weeks, is based on random-
ized control trials. However, a substantial number of patients require delays or reductions on this schedule.
The Cancer Centre of Southeastern Ontario (CCSEO) has historically administered chemotherapy every
4 weeks. We analyzed survival outcomes of our cohort. All ovarian cancer patients treated with chemother-
apy at the CCSEO from 1995 to end-2002 were included in this study. Overall survival and progression-free
survival were calculated from initiation of chemotherapy using the Kaplan–Meier technique and log-rank
tests. Cox regression analysis was used to adjust for age and disease stage. A total of 171 patients were
treated with chemotherapy (cisplatin–paclitaxel or carboplatin–paclitaxel), of which 144 received chemother-
apy every 4 weeks and 27 every 3 weeks. Median progression-free survival was 19.2 months for the group
treated every 4 weeks vs 13.2 months for the 3-weekly group. Median overall survival was 36.5 months
compared to 27.1 months, respectively. Trends favored treatment every 4 weeks. In early-stage disease,
5-year overall survival was 74% and 5-year progression-free survival was 68%. Administration of platinum–
paclitaxel chemotherapy every 4 weeks did not reduce survival of ovarian cancer patients. Importantly,
median survival is favorable compared to results from landmark trials where patients were treated every
3 weeks. These results suggest that decreasing the frequency of chemotherapy cycles does not decrease
survival. Prospective trials would be required to compare quality of life and cost-effectiveness.
KEYWORDS: carboplatin, chemotherapy, dose density, ovarian neoplasm, paclitaxel.
Ovarian cancer is the fifth-leading cause of cancer death
among North American women with a 5-year survival
rate of 38–44%(1,2). The current standard of care for
women newly diagnosed with ovarian cancer at stage
IC or above, or with lower stage but high-risk histology,
is surgery followed by adjuvant carboplatin–paclitaxel
combination chemotherapy. This choice of carboplatin
combination chemotherapy, as borne out by large ran-
domized controlled trials over the past decade, offers
the same optimal efficacy as a cisplatin–paclitaxel regi-
men, but has a more tolerable side effect profile(3,4).
Defining the optimal dose intensities, frequency,
and number of total cycles of adjuvant platinum/pac-
litaxel combinations has been less rigorously investi-
gated. Higher dose density regimens have been
described for platinum-based chemotherapy (none
combined with paclitaxel), and overall do not lend
support for survival benefit with these higher dose
regimens(5). The current consensus treatment schedule
consists of carboplatin area under the curve (AUC)
5–7.5 plus paclitaxel 175 mg/m2administered during
six treatment courses every 3 weeks(6,7). At our institu-
tion, chemotherapy for ovarian cancer has been
administered every 4 weeks, with the reasoning that it
may be better tolerated by patients. There is limited
evidence that treatment every 4 weeks is comparable
to 3-weekly cycles based on a phase II trial reported
Address correspondence and reprint requests to: Dr. James J. Biagi,
MD, FRCP(C), Cancer Centre of Southeastern Ontario, 25 King
St. W., Kingston, ON K7L 5P9 Canada. Email: firstname.lastname@example.org
#2007, Copyright the Authors
Journal compilation#2007, IGCS and ESGO
Int J Gynecol Cancer 2008, 18, 8–13
population, the increased aggressiveness of treatment
that may be associated with randomized prospective
trials, and in keeping with the principle of ‘‘do less
harm’’ that initially guided the choice of a 4-weekly
dosing regimen at our center. Our study was not de-
signed to evaluate performance status and quality of
life measures, two important variables that may be
more valuable than toxicity outcomes to demonstrate
whether chemotherapy every 4 weeks does improve
patient well-being without compromising survival.
The limitations of our study include its retrospective
nature and small sample size of patients treated every
3 weeks. Nevertheless, our population of patients rep-
resents a real cohort from which we can draw relevant
inferences, and our database has proven a useful tool
to evaluate outcomes for our center. In the future,
a prospectively collected database, where a standard-
ized system for recording toxicity data is in place,
would allow for a more complete analysis of chemo-
Our hypothesis that chemotherapy every 4 weeks
does not affect survival, while reducing toxicity, has
widespread implications for patients and caregivers
alike. Cost-effectiveness may improve if fewer hospi-
talizations for chemotherapy-associated toxicity, and
less frequent use of granulocyte-colony stimulating
factor result from a 4-weekly administration schedule.
Our hypothesis may also extend to intraperitoneal
chemotherapy, where a survival benefit compared to
standard chemotherapy was recently demonstrated in
a clinical trial(18). In this landmark study, patients were
treated every 3 weeks, but fewer than 50% of patients
were able to complete the planned six cycles of intra-
peritoneal chemotherapy due to high leucopenia rates
and subsequent infections. Our hypothesis may thus
extend to intraperitoneal chemotherapy delivery in
that patients treated every 4 weeks may have lower
neutropenia and infection rates: a decrease in dose
density may then allow maintenance of planned dose
In conclusion, our study demonstrates that survival
outcomes for ovarian cancer patients treated with
4 weeks are not different compared to those observed
for patients treated every 3 weeks and as reported by
the literature in larger studies. However, the rates of
toxicities requiring dose modifications are not reduced
in our study population when compared to patients
treated every 3 weeks. Further work is necessary to
determine whether decreasing the frequency of che-
motherapy improves patient quality of life without
The authors would like to thank Angela Cook for
assistance with data gathering.
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Accepted for publication March 15, 2007
Effects of decreased dose density on survival of ovarian cancer patients
#2007 IGCS and ESGO, International Journal of Gynecological Cancer 18, 8–13