phase III trial is studying gemcitabine and oxaliplatin - pancreatic
- From: J <studras@xxxxxxxx>
- Date: Sun, 15 Jan 2006 08:33:18 -0500
http://www.aetna.com/cpb/data/CPBA0683.html
linical Policy Bulletins
Number: 0683
(Updated)
Subject: Oxaliplatin (Eloxatin)
Reviewed: January 13, 2006
Important Note
This Clinical Policy Bulletin expresses Aetna's determination of whether
certain services or supplies are medically necessary, experimental and
investigational, or cosmetic. Aetna has reached these conclusions based
upon a review of currently available clinical information (including
clinical outcome studies in the peer-reviewed published medical
literature, regulatory status of the technology, evidence-based guidelines
of public health and health research agencies, evidence-based guidelines
and positions of leading national health professional organizations, views
of physicians practicing in relevant clinical areas, and other relevant
factors). Aetna makes no representations and accepts no liability with
respect to the content of any external information cited or relied upon in
this Bulletin. The discussion, analysis, conclusions and positions
reflected in this Bulletin, including any reference to a specific
provider, product, process or service by name, trademark, manufacturer,
constitute Aetna's opinion and are made without any intent to defame.
Aetna expressly reserves the right to revise these conclusions as clinical
information changes, and welcomes further relevant information including
correction of any factual error. Each benefit plan defines which services
are covered, which are excluded, and which are subject to dollar caps or
other limits. Members and their providers will need to consult the
member's benefit plan to determine if there are any exclusions or other
benefit limitations applicable to this service or supply. The conclusion
that a particular service or supply is medically necessary does not
constitute a representation or warranty that this service or supply is
covered (i.e., will be paid for by Aetna) for a particular member. The
member's benefit plan determines coverage. Some plans exclude coverage for
services or supplies that Aetna considers medically necessary. If there is
a discrepancy between this policy and a member's plan of benefits, the
benefits plan will govern. In addition, coverage may be mandated by
applicable legal requirements of a State, the Federal government or CMS
for Medicare and Medicaid members. CMS's Coverage Database can be found on
the following website: http://www.cms.hhs.gov/center/coverage.asp.
Policy
1. Aetna considers oxaliplatin injection (Eloxatin) medically necessary
for treatment of persons with advanced carcinoma of the colon or rectum,
including use as adjuvant treatment in persons who have undergone complete
resection of their primary tumor.
2. Aetna considers oxaliplatin injection medically necessary for
treatment of persons with advanced gastric carcinoma.
3. Aetna considers oxaliplatin injection medically necessary for
treatment of persons with adenocarcinoma of the pancreas and for ampullary
and periampullary carcinomas.
4. Aetna considers oxaliplatin injection experimental and
investigational for the treatment of members with esophageal cancer,breast
cancer, or other types of cancers since its effectiveness for these
indications has not been established.
See also CPB 371 - Brachytherapy, CPB 375 - Photodynamic Therapy for
Cancer, CPB 516 - Colorectal Cancer Screening, and CPB 535 - Virtual
Colonoscopy.
Background
Oxaliplatin for Pancreatic Cancer:
Systemic chemotherapy with 5-FU-based combinations had minimal impact on
natural history of pancreatic cancer. Several new agents have been
identified over the past decade. Favorable adverse effect profile and
tolerability are clear advantages of single-agent gemcitabine and enable
its incorporation into combination regimens. Currently, the most widely
used regimens involve combination partners such as 5-FU, cisplatin, and
docetaxel. Recently, combination therapy using gemcitabine and oxaliplatin
has been studied in the treatment of patients with advanced or metastatic
pancreatic adenocarcinoma (ACA).
In a phase II clinical study, Alberts, et al. (2003) examined the
effectiveness of gemcitabine and oxaliplatin in patients (n = 47) with
advanced or metastatic pancreatic ACA. Oxaliplatin was given intravenously
on day 1 and gemcitabine intravenously on days 1 and 8 of a 3-week cycle.
The primary endpoint of the trial was 6-month survival. Secondary
endpoints included response rate, overall survival, median time to
progression and toxicity. Of the 46 patients assessed for the primary
endpoint, 50 % lived for greater than or equal to 6 months. The median
time to progression was 4.53 months. Five confirmed responses were seen
with a median duration of response of 2.7 months. Overall, the treatment
was well tolerated. However, one patient died as a result of
treatment-related hemolytic uremic syndrome. The authors concluded that
gemcitabine and oxaliplatin, at doses of 1000 mg/m2 and 100 mg/m2,
respectively, showed moderate activity in patients with pancreatic ACA.
In a phase II clinical study, Conroy, et al. (2005) examined the
effectiveness of oxaliplatin with irinotecan, leukovorin and
5-fluorouracil in chemotherapy-naive patients with histologically proven
pancreatic ACA. Patients were treated every two weeks. Forty-seven
patients were entered, and 46 received treatment. Thirty-five patients
(76%) had metastatic disease. Subjects received a median of eight cycles
(range, one to 24 cycles). Grade 3 to 4 neutropenia occurred in 52% of
patients, including two patients with febrile neutropenia. Other relevant
toxicities included grade 3 to 4 nausea (20%), vomiting (17%), and
diarrhea (17%) and grade 3 neuropathy (15%). The confirmed response rate
was 26% (95% CI, 13% to 39%), including 4% complete responses. Median time
to progression was 8.2 months (95% CI, 5.3 to 11.6 months), and median
overall survival was 10.2 months (95% CI, 8.1 to 14.4 months). Between
baseline and end of treatment, patients had improvement in all quality of
life functional scales, except cognitive functioning.
Decreaux reported on the results of a randomized phase II, open-label
multicenter study evaluating oxaliplatin alone, infusional 5-fluorouracil
alone and an oxaliplatin/infusional 5-FU combination in untreated,
advanced pancreatic carcinoma. Sixty-three patients were treated: 17
patients received oxaliplatin, 31 patients received oxaliplatin combined
with 5-FU, and 15 patients received 5-FU, with a median of three, six and
two cycles per patient, respectively. All responses (three partial
responses) occurred in subjects receiving the oxaliplatin/5-FU combination
therapy (10% response rate). Five of 32 patients evaluable for clinical
benefit were responders (oxaliplatin, 14%; oxaliplatin/5-FU combination,
21%). Median time to progression and overall survival were higher in the
combination arm (4.2 and 9.0 months, respectively) than either
single-agent arm (oxaliplatin, 2.0 and 3.4 months; 5-FU, 1.5 and 2.4
months, respectively). The investigators concluded that, with a 10%
response rate, median overall survival of 9 months and an encouraging
safety profile, the oxalliplatin/5-FU combination is effective, appears
superior to infusional 5-FU and warrants further studies in pancreatic
adenocarcinoma patients.
Results of a phase III clinical study comparing gemcitabine in combination
with oxaliplatin GEMOX) versus gemcitabine alone in this patient
population are not yet available. Louvet reported on interim results of
the GEMOX trial, but only in abstract form. The abstract notes that, since
enrollment in the trial is still open at the time of the abstract, no
efficacy results could be disclosed.
The National Comprehensive Cancer Network (2004) guidelines on the
management of pancreatic cancer state that gemcitabine either alone or in
combination with other chemotherapeutic agents are the preferred first
line treatment of pancreatic cancer. The NCCN Panel has stated that
combinations of gemcitabine with oxaliplatin, cisplatin, or irinotecan are
appropriate for combination therapy. The NCCN Panel also acknowledged
that, historically, combination chemotherapy has not appeared to be
superior to monotherapy in the era of 5-fluorouracil (FU)-based therapy.
However, because gemcitabine is superior to bolus 5-FU when efficacy end
points of survival and relief from symptoms are used, it is now combined
with other chemotherapeutic agents. The Eastern Cooperative Oncology Group
(ECOG) has compared gemcitabine monotherapy with gemcitabine and bolus
5-FU in patients with advanced pancreatic cancer; no statistically
significant survival advantage was observed for patients receiving the
combination. However, gemcitabine has been investigated in combination
with potentially synergistic agents, such as cisplatin, oxaliplatin, and
irinotecan. Although response rates and time to progression (with platinum
regimens) have appeared superior when gemcitabine is combined with these
agents, no clear survival advantage has been demonstrated. The NCCN Panel
considers the use of gemcitabinebased combination therapy as reasonable
only for patients with good performance status (ECOG 0 or 1) who are
interested in pursuing more aggressive therapy outside a clinical trial.
http://www.clinicaltrials.gov/ct/gui/show/NCT00075452
Gemcitabine With or Without Oxaliplatin in Treating Patients With Locally
Advanced or Metastatic Unresectable Pancreatic Adenocarcinoma
This study is no longer recruiting patients.
Sponsored by: Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00075452
Purpose
RATIONALE: Drugs used in chemotherapy, such as gemcitabine and
oxaliplatin, work in different ways to stop tumor cells from dividing so
they stop growing or die. It is not yet known whether gemcitabine is more
effective with or without oxaliplatin in treating pancreatic
adenocarcinoma.
PURPOSE: This randomized phase III trial is studying gemcitabine and
oxaliplatin to see how well they work compared to gemcitabine alone in
treating patients with locally advanced or metastatic unresectable
pancreatic adenocarcinoma.
Study ID Numbers: CDR0000346480; FRE-GERCOR-GEM-GEMOX/D00-3; EU-20324;
NCT00075452
Last Updated: December 8, 2005
Record first received: January 9, 2004
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