Thursday, March 10, 2011

Carbo vs RT for stage I seminoma

In JCO this week:

the Carbo vs RT trial from the MRC and EORTC is updated with 5 year results - the short of it is that there is no difference in disease control, and a reduction in the rate of contralateral GCT.

Link and abstract:

Randomized Trial of Carboplatin Versus Radiotherapy for Stage I Seminoma: Mature Results on Relapse and Contralateral Testis Cancer Rates in MRC TE19/EORTC 30982 Study (ISRCTN27163214) [Urologic Oncology]: "Purpose

Initial results of a randomized trial comparing carboplatin with radiotherapy (RT) as adjuvant treatment for stage I seminoma found carboplatin had a noninferior relapse-free rate (RFR) and had reduced contralateral germ cell tumors (GCTs) in the short-term. Updated results with a median follow-up of 6.5 years are now reported.

Patients and Methods

Random assignment was between RT and one infusion of carboplatin dosed at 7 x (glomerular filtration rate + 25) on the basis of EDTA (n = 357) and 90% of this dose if determined on the basis of creatinine clearance (n = 202). The trial was powered to exclude a doubling in RFRs assuming a 96-97% 2-year RFR after radiotherapy (hazard ratio [HR], approximately 2.0).


Overall, 1,447 patients were randomly assigned in a 3-to-5 ratio (carboplatin, n = 573; RT, n = 904). RFRs at 5 years were 94.7% for carboplatin and 96.0% for RT (RT-C 90% CI, 0.7% to 3.5%; HR, 1.25; 90% CI, 0.83 to 1.89). One death as a result of seminoma (in RT arm) occurred. Patients receiving at least 99% of the 7 x AUC dose had a 5-year RFR of 96.1% (95% CI, 93.4% to 97.7%) compared with 92.6% (95% CI, 88.0% to 95.5%) in those who received lower doses (HR, 0.51; 95% CI, 0.24 to 1.07; P = .08). There was a clear reduction in the rate of contralateral GCTs (carboplatin, n = 2; RT, n = 15; HR, 0.22; 95% CI, 0.05 to 0.95; P = .03), and elevated pretreatment follicle-stimulating hormone (FSH) levels (> 12 IU/L) was a strong predictor (HR, 8.57; 95% CI, 1.82 to 40.38).


These updated results confirm the noninferiority of single dose carboplatin (at 7 x AUC dose) versus RT in terms of RFR and establish a statistically significant reduction in the medium term of risk of second GCT produced by this treatment.


Kyphoplasty for Malignant Compression Fractures

An interesting arcticle in the Lancet Oncology reporting a randomized trial on using kyphoplasty for malignant compression fractures.

What they show is that kyphoplasty pretty safe and effective, and I am encouraged by the fact that the interventional radiology literature on these sorts of maneuvers is improving with prospective and randomized evaluations of care. What it doesn't show is that it should replace RT in these situations, as the control arm was simply whatever care the treating physicians wished to deliver. The authors do skirt the subject of the downsides of RT in their discussion, suggesting that this could be a replacement, but I would view that with significant skepticism. I would instead look at these as complimentary treatments, as there is no doubt that kyphoplasty holds the promise of much more rapid pain relief, and RT actually treats the tumor responsible for the fracture in the first place.