Saturday, April 07, 2012
abstract - Gynecologic Oncology - Outcome of immediate re-operation or interval debulking after chemotherapy at a gynecologic oncology center after initially incomplete cytoreduction of advanced ovarian cancer
Gynecologic Oncology - Outcome of immediate re-operation or interval debulking after chemotherapy at a gynecologic oncology center after initially incomplete cytoreduction of advanced ovarian cancer
Background
Prognosis
in advanced ovarian cancer is largely determined by completeness of
tumor resection achieved during primary surgery. Incomplete initial
debulking occurs frequently in non-specialized centers and there is an
ongoing discussion about the best time for re-surgery after referral to
tertiary centers.
Methods
Patients
with advanced epithelial ovarian cancer (FIGO IIIB-IV) admitted between
1999 and 2007 who had primary incomplete surgery including those with
initiated chemotherapy at outside institution were included. Surgical
results, morbidity and prognosis were evaluated in patients with
immediate re-operation before chemotherapy and those with interval
debulking.
Results
48
eligible patients were identified in our tumor registry. Self-referral
by patient was the most frequent mode of admission (n = 21, 43.8%). 22
patients (45.8%) patients underwent immediate re-surgery and 26 patients
(54.2%) had an interval debulking after chemotherapy. In 12 patients
(54.5%), macroscopically complete tumor removal could be achieved by
immediate re-operation and in 17 patients (65.4%) after chemotherapy.
Major complications were observed more frequently in patients with
interval debulking (26.9 vs. 9.1%, p = 0.324). Median overall survival
time was 53 and 34 months (p = 0.110) after immediate and delayed
re-operation, respectively.
Conclusions
Upfront
re-operation before start of chemotherapy is feasible and successful in
an expertise referral centre in more than half of patients with
incomplete primary surgery elsewhere. Complete resection even after
initial incomplete debulking could improve outcome. Therefore, referral
to expertise centers in those patients should be considered.
Progression-free survival and overall survival showed a non-significant
trend and complication rate a remarkable advantage in favor of upfront
re-operation.
Keywords
- primary ovarian cancer;
- cytoreductive surgery;
- interval debulking surgery
abstract: Cochrane Review: Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer
Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer [Cochrane Database Syst Rev. 2012] - PubMed - NCBI
Cochrane Database Syst Rev. 2012 Mar 14;3:CD004706.
Abstract
BACKGROUND:
Epithelial ovarian cancer is diagnosed in 4500 women in the UK each year of whom 1700 will ultimately die of their disease.Of all cases 10% to 15% are diagnosed early when there is still a good possibility of cure. The treatment of early stage disease involves surgery to remove disease often followed by chemotherapy. The largest clinical trials of this adjuvant therapy show an overall survival (OS) advantage with adjuvant platinum-based chemotherapy but the precise role of this treatment in subgroups of women with differing prognoses needs to be defined.OBJECTIVES:
To
systematically review the evidence for adjuvant chemotherapy in early
stage epithelial ovarian cancer to determine firstly whether there is a
survival advantage of this treatment over the policy of observation
following surgery with chemotherapy reserved for treatment of disease
recurrence, and secondly to determine if clinical subgroups of differing
prognosis based on histological sub-type, or completeness of surgical
staging, have more or less to gain from chemotherapy following initial
surgery.
SEARCH METHODS:
We performed an electronic search using the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 3), MEDLINE (1948 to Aug week 5, 2011) and EMBASE (1980 to week 36, 2011). We developed the search strategy using free-text and medical subject headings (MESH).SELECTION CRITERIA:
We selected randomised clinical trials that met the inclusion criteria set out based on the populations, interventions, comparisons and outcome measures.DATA COLLECTION AND ANALYSIS:
Two review authors independently extracted data and assessed trial quality. Disagreements were resolved by discussion with a third review author. We performed random-effects meta-analyses and subgroup analyses.MAIN RESULTS:
Five randomised controlled trials (RCTs), enrolling 1277 women, with a median follow-up of 46 to 121 months, met the inclusion criteria. Four trials were included in the meta-analyses and we considered them to be at a low risk of bias. Meta-analysis of five-year data from three trials indicated that women who received adjuvant platinum-based chemotherapy had better overall survival (OS) than those who did not (1008 women; hazard ratio (HR) 0.71; 95% confidence interval (CI) 0.53 to 0.93). Likewise, meta-analysis of five-year data from four trials indicated that women who received adjuvant chemotherapy had better progression-free survival (PFS) than those who did not (1170 women; HR 0.67; 95% CI 0.53 to 0.84). The trials included in these meta-analyses gave consistent estimates of the effects of chemotherapy. In addition, these findings were robust over time (10-year PFS: two trials, 925 women; HR 0.67; 95% CI 0.54 to 0.84).Subgroup analysis suggested that women who had optimal surgical staging of their disease were unlikely to benefit from adjuvant chemotherapy (HR for OS 1.22; 95% CI 0.63 to 2.37; two trials, 234 women) whereas those who had sub-optimal staging did (HR for OS 0.63; 95% CI 0.46 to 0.85; two trials, 772 women).
One trial showed a benefit from adjuvant chemotherapy among women at high risk (HR for OS 0.48; 95% CI 0.32 to 0.72) but not among those at low/medium risk (HR for OS 0.95; 95% CI 0.54 to 1.66). However, these subgroup findings could be due to chance and should be interpreted with caution.
AUTHORS' CONCLUSIONS:
Adjuvant platinum-based chemotherapy is effective in prolonging the survival of the majority of patients who are assessed as having early (FIGO stage I/IIa) epithelial ovarian cancer. However, it may be withheld from women in whom there is well-differentiated encapsulated unilateral disease (stage 1a grade 1) or those with comprehensively staged Ib, well or moderately differentiated (grade 1/2) disease.Others with unstaged early disease or those with poorly differentiated tumours should be offered chemotherapy. A pragmatic approach may be necessary in clinical settings where optimal staging is not normally performed/achieved. In such settings, adjuvant chemotherapy may be withheld from those with encapsulated stage Ia grade 1 serous and endometrioid carcinoma and offered to all others with early stage disease.
Fulltext | Epithelial ovarian cancer: A feasible plan for adjunctive treatment using simultaneous acyclovir, ambrisentan, captopril, disulfiram, fluvoxamine-augmented ramelteon, icatibant, imiquimod peritoneal lavage, and plerixafor | Journal of Cancer Therapeutics & Research
Fulltext | Epithelial ovarian cancer: A feasible plan for adjunctive treatment using simultaneous acyclovir, ambrisentan, captopril, disulfiram, fluvoxamine-augmented ramelteon, icatibant, imiquimod peritoneal lavage, and plerixafor | Journal of Cancer Therapeutics & Research
Conclusion
To improve the prognosis in EOC an effort to comprehensively block growth factors that have been identified as active in human EOC as suggested in this paper may prove fruitful. Past research indicates that several already-approved and marketed drugs might do this. The nine drugs have no clearly discernable interaction with each other and none would be expected to interfere with concomitant current cytotoxic chemotherapy regimens although such cannot be excluded. Given the safety of the nine drugs individually, and the poor prognosis of an EOC seeded peritoneum, the risk of unexpected side effects or interaction I believe is worth taking.
abstract: Assumptions of Expected Benefits in Randomized Phase III Trials Evaluating Systemic Treatments for Cancer
Blogger's Note: also reference related commentary: " Why Do Phase III Clinical Trials in Oncology Fail so Often?
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Assumptions of Expected Benefits in Randomized Phase III Trials Evaluating Systemic Treatments for Cancer
open access: Why Do Phase III Clinical Trials in Oncology Fail so Often?
Why Do Phase III Clinical Trials in Oncology Fail so Often?
"Achieving success in the development of a cancer drug continues to be challenging. Given the increasing costs (1) and the small number of drugs that gain regulatory approval (2), it is crucial to understand these failures. In this issue of the Journal, Gan et al. (3)
reviewed 235 recently published phase III randomized clinical trials
(RCTs). They report that 62% of the trials did not
achieve results with statistical significance. Trying
to explain the high failure rate, they note the actual magnitude of
benefit achieved in a clinical trial (designated B) is
nearly always less than what was predicted at the time the trial was
designed (designated δ) and conclude, “investigators
consistently make overly-optimistic assumptions regarding treatment
benefits
when designing RCTs.”
But really should we be surprised that phase III trials, the venue for detecting “small” differences, so often disappoint?
Almost by definition, phase III studies are designed to detect small differences (4,5).
The problem is that small has given way to “marginal” as outcomes have
fallen below our already modest expectations. And
who or what is to blame? Are investigators really
overly optimistic regarding experimental therapies and, as the authors
suggest,
responsible for the large number of negative studies?
Although we agree that optimism regarding clinical benefit may lead
to an underpowered trial, we disagree that optimistic
investigators are those we should blame. We would ask, how do Gan et
al. (3) define optimism? Where do they place the line between an optimistic and a realistic expectation?.........
open access: online book - Ovarian cancer: the recognition and initial management of ovarian cancer - NICE
Ovarian cancer: the recognition and initialmanagement of ovarian cancer
This guidance updates and replaces recommendation 1.7.4 in
‘Referral guidelines for suspected cancer’ (NICE clinical guideline
27; published June 2005).
Full Guideline (148 pages)
April 2011
Developed for NICE by the National Collaborating Centre for Cancer
Published by the National Collaborating Centre for Cancer (2nd Floor, Front Suite, Park House, Greyfriars Road, Cardiff,
CF10 3AF) at Velindre NHS Trust, Cardiff, Wales.
First published 2011
©2011 National Collaborating Centre for Cancer
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