Carboplatin as Effective as Radiation in Preventing Relapse in Testicular Cancer

Roxanne Nelson

June 10, 2008

June 10, 2008 (Chicago, Illinois) — A single dose of carboplatin appears to be as effective as adjuvant radiotherapy in preventing disease recurrence among men with stage 1 seminoma after orchiectomy. In an abstract presented here at the American Society of Clinical Oncology (ASCO) 44th Annual Meeting, researchers reported that carboplatin was also significantly more effective than radiotherapy in preventing contralateral testicular germ-cell cancers.

"A single dose of carboplatin produced a significant 78% reduction in contralateral tumors in 5 years," said lead author Tim Oliver, MD, professor emeritus of medical oncology at St. Bartholomew's Hospital, in London, United Kingdom.

Radiation has been the standard of care for about 60 years, but as patients have been followed more carefully, there has been a growing awareness that men who undergo adjuvant radiotherapy have excess mortality rates, compared with men of the same age in the general population, explained Dr. Oliver.

"At least half of the excess mortality was due not to radiation-induced cancers, but to increased cardiac and cerebrovascular disease," he said. "About a third or half of cancers that do occur are not in the radiation field."

These findings demonstrated a need for alternative treatment, and reducing radiation dosage has been an option, as is surveillance after primary orchiectomy with no additional treatment. Although a safe follow-up for many of these patients, surveillance has a higher relapse rate (about 15% to 20%) than radiation (5%).

The use of single-agent carboplatin has shown promising results, similar to those obtained with radiotherapy; seminomas appear to have a greater sensitivity to platinum drugs than nonseminomas.

In the largest trial that has ever been conducted in testicular cancer, a total of 1477 patients with stage 1 seminoma were recruited from 70 hospitals in 14 countries throughout Europe. Between 1996 and 2001, patients were randomized to 1 of 2 treatments: carboplatin dosed at 7 times (glomerular filtration rate + 25 mL/min per 1.73 m2) if based on ethylenediamine tetraacetic acid (n = 357) and 90% of that dose if based on creatinine clearance (n = 202); or standard radiotherapy.

The primary end point of the study was relapse rates in patients treated with adjuvant radiotherapy and in patients treated with a single dose of carboplatin. "We wanted to show that carboplatin was a safe alternative," said Dr. Oliver.

The results of the trial were initially presented at the 2004 ASCO annual meeting, after a median follow-up of 4 years. At that time, the rates of cancer recurrence and second cancers were comparable between the 2 groups. There were 32 recurrences of the original tumor in the radiotherapy group, and 27 recurrences in the carboplatin group. Secondary cancers occurred in 11 patients in the radiotherapy group and in 3 patients in the carboplatin group.

Because the researchers felt that a longer follow-up was warranted, the study continued; the results after a median of 6.5 years of follow-up are reported here. The relapse-free rates at 5 years were 95% for patients in the carboplatin group and 96% for those in the radiotherapy group. Patients who received the full dose of carboplatin had a relapse-free rate of 96.1%, which was identical to that of radiotherapy. Only 1 seminoma-related death was reported; it occurred in the radiotherapy group.

One of the more significant findings, noted Dr. Oliver, was the superiority of carboplatin in preventing contralateral testicular germ-cell cancers. There were 2 contralateral cancers reported in the carboplatin group and 15 in the radiotherapy group, with a hazard ratio of 0.22 (95% confidence interval, 0.05, 0.95; P = .03).

High levels of pretreatment follicle-stimulating hormone (>12 IU/L) were associated with an increased risk of developing a second germ-cell cancer, and patients with larger tumors (>4 cm) had poorer relapse-free rates.

"With a mature 6.5 years of follow-up, we found that single-dose carboplatin is safe, less acutely toxic, and as effective as radiation," concluded Dr. Oliver. "But before safety can be unequivocally confirmed, patients will need to be followed for about 20 years.

Not Standard of Care Just Yet

In a discussion of the study, George J. Bosl, MD, chair of the department of medicine at Memorial Sloan-Kettering Cancer Center, in New York, New York, pointed out that, currently, cure rates for stage 1 seminoma are very high, and that must be maintained.

"It seems that, according to this study, carboplatin appears to be a reasonable third option, with the other 2 being radiation and surveillance," he said. "I think carboplatin is an option, but I would not say it's the standard of care."

He explained that secondary malignant neoplasms exist for both treatments, and a much longer follow-up is needed to evaluate the association between carboplatin and second cancers.

"We need more long-term follow-up before we can recommend carboplatin over radiation," he said. "We want to make sure that we obtain the maximum cure with the minimal toxicity."

Surveillance is the option with the least amount of toxicity, he said. "When counseling patients, we have to explain that each therapy has its own risks."

The study was funded by the Medical Research Council, United Kingdom.

American Society of Clinical Oncology (ASCO) 44th Annual Meeting: Abstract 1. Presented May 31, 2008.

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