2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

CHEMOTHERAPY FOR OVARIAN CANCER
which patients with stage III/IV ovarian, tubal, or primary
peritoneal cancer, were allocated to receive either primary
debulking surgery followed by eight cycles of chemotherapy
or to receive neoadjuvant chemotherapy with four cycles of
chemotherapy followed by interval debulking surgery plus
an additional four cycles of chemotherapy. This study is
designed as a noninferiority trial with 300 patients in total.
This trial completed accrual in 2011.
The ultimate goal of neoadjuvant chemotherapy is to
minimize the invasiveness of surgical treatment without
jeopardizing its efficacy. The most successful example is
breast-conserving surgery after neoadjuvant chemotherapy.
In the EORTC55791 trial, the survival was same between
primary debulking surgery group and neoadjuvant chemotherapy
group, but it was not fully analyzed how they could
minimize the invasiveness of surgery between primary and
interval surgery.
The remaining questions on neoadjuvant chemotherapy
include: 1) accurate selection of candidate patients, 2) duration
of chemotherapy before interval debulking surgery, 3)
selection and duration of adjuvant therapy after interval
debulking surgery, and finally 4) whether the failure to
achieve optimal cytoreductive surgery is to the result of the
surgeon’s skill or biology of the cancer.
For the first question, JCOG investigators conducted a
prospective feasibility study on the selection of the patients
who would be suitable for neoadjuvant chemotherapy
Authors’ Disclosures of Potential Conflicts of Interest
Author
Employment or
Leadership
Positions
Consultant or
Advisory Role
Keiichi Fujiwara Amgen;
Boehringer
Ingelheim;
GlaxoSmithKline;
Zeria Pharma
Noriyuki Katsumata*
Takashi Onda*
*No relevant relationships to disclose.
1. Stuart GC, Kitchener H, Bacon M, et al. 2010 Gynecologic Cancer
InterGroup (GCIG) consensus statement on clinical trials in ovarian cancer:
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2. Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab
in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:
2473-2483.
3. Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab
in ovarian cancer. N Engl J Med. 2011;365:2484-2496.
4. Thigpen T, duBois A, McAlpine J, et al. First-line therapy in ovarian
cancer trials. Int J Gynecol Cancer. 2011;21:756-1762.
5. Vergote I, Trope CG, Amant F, et al. Neoadjuvant chemotherapy or
primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010;363:
943-953.
6. Norton L. Theoretical concepts and the emerging role of taxanes in
adjuvant therapy. Oncologist. 2001; 3:30-35 (suppl).
7. Seidman AD, Berry D, Cirrincione C, et al. Randomized phase III trial of
weekly compared with every-3-weeks paclitaxel for metastatic breast cancer,
with trastuzumab for all HER-2 overexpressors and random assignment to
trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and
Leukemia Group B protocol 9840. J Clin Oncol. 2008;26:1642-1649.
8. Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant
treatment of breast cancer. N Engl J Med. 2008;358:1663-1671.
(JCOG0206). 21 They assessed the accuracy of clinical diagnosis
on the basis of imaging tests, cytology from ascites,
pleural effusion or tumor, and tumor markers (cancer antigen
[CA]-125 � 200 U/mL and Carcinoembryonic antigen
[CEA] � 20 ng/mL). The diagnosis was confirmed by diagnostic
laparoscopy and these results showed that patients
can be correctly diagnosed as having ovarian, fallopian tube,
or primary peritoneal carcinoma with greater than 90%
accuracy by clinical diagnoses on the basis of findings
including cytology, according to Bayesian statistical methods.
Other questions, however, have not been investigated
prospectively. We can hypothesize that the greater the
number of cycles of neoadjuvant chemotherapy, the less
invasive the interval surgery would be because the disseminated
tumor could be eliminated by the chemotherapy.
However, meta-analysis of retrospective studies reported
that increasing the number of chemotherapy cycles before
interval surgery would negatively affect survival. 16,22 It is
hoped that these important questions will be answered
prospectively in the near future.
Conclusion
The important concept of dose-dense chemotherapy and
neoadjuvant chemotherapy in the treatment of ovarian
cancer has been tested in phase III trials 5,9 and is a great
influence on clinical practice.
Stock
Ownership Honoraria
REFERENCES
Bristol-Myers
Squibb; Chugai
Pharma;
Janssen
Oncology;
Nihonkayaku;
Sanofi; Taiho
Pharmaceutical
Research
Funding
Expert
Testimony
Other
Remuneration
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a week in combination with carboplatin every 3 weeks for advanced ovarian
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1331-1338.
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nonmetastatic breast cancer: a systematic review and meta-analysis of
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16. Bristow RE, Chi DS. Platinum-based neoadjuvant chemotherapy and
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