EORTC (2010)

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Clinical Question

In patients with stage IIIC or IV epithelial ovarian carcinoma, fallopian-tube carcinoma, or primary peritoneal carcinoma, is neoadjuvant platinum-based chemotherapy followed by debulking surgery non-inferior to primary debulking surgery followed by platinum-based chemotherapy for overall survival?

Bottom Line

Neoadjuvant chemotherapy followed by debulking surgery is not inferior to primary debulking surgery followed by chemotherapy in terms of overall survival for patients with stage IIIC or IV ovarian carcinoma.

Major Points

Several small and large randomized trials in diabetics had previously suggested a sizable benefit of tight glycemic control in reducing cardiovascular risk. The ACCORD trial was the largest study of its kind and demonstrated that not only does euglycemia (ie, HbA1c <6%) not reduce cardiovascular risk, it also is associated with a trend towards increased mortality.

Guidelines

Design

  • Multicenter, double-blind, parallel-group, randomized, controlled trial
  • N=10,251
    • Intensive (n=5,128)
    • Standard (n=5,123)
  • Setting: 77 centers in Canada and the United States
  • Enrollment: January to June 2001, February 2003 to October 2005
  • Mean follow-up: 3.5 years
  • Analysis: Intention-to-treat
  • Primary outcome:

Population

Inclusion Criteria

  • Type 2 diabetes mellitus
  • Hemoglobin A1c ≥7.5%
  • Age 40-79 years with CAD or 55-79 years with
  • Anatomical evidence of significant atherosclerosis
  • Albuminuria
  • LVH
  • ≥2 cardiovascular risk factors (dyslipidemia, HTN, current smoking, obesity)

Exclusion Criteria

  • Frequent or recent serious hypoglycemic events
  • Unwillingness to perform home glucose monitoring or insulin injections
  • BMI >45
  • Cr >1.5mg/dl
  • Serious illness

Baseline Characteristics

  • Mean age: 72 years
  • Mean BMI: 28
  • Mean HbA1c: 8.8%
  • Units of insulin: 14 units/day

Interventions

  • Randomized to intensive (targeting HbA1c <6%) or standard (HbA1c 7-7.9%) glycemic therapy

    • Then 46% were randomized to intensive (SBP <120) vs. standard (SBP <140) blood pressure therapy
    • Remaining 54% randomized to fenofibrate vs. placebo; all received statin
  • Intensive glycemic control group attended monthly visits for 4 months, then every 2 months, with additional visits and telephone calls as needed
  • Standard therapy group had glycemic control visits every 4 months

Outcomes

Comparisons are intensive therapy vs. standard therapy.

Primary Outcomes

Annual rate of nonfatal MI or nonfatal stroke or cardiovascular death
2.11% vs. 2.29% (HR 0.90; 95% CI 0.78-1.04; P=0.16)

Secondary Outcomes

Annual rate of death from any cause
1.41% vs. 1.14% (HR 1.22; 95% CI 1.01-1.46; P=0.04)
Annual rate of cardiovascular death
0.79% vs. 0.56% (HR 1.35; 95% CI 1.04-1.76; P=0.02)

Subgroup Analysis

Adverse Events

Criticisms

Funding

Further Reading