Curing metastatic testicular cancer

Lawrence Einhorn

Indiana University Medical Center, 535 Barnhill Drive, RT 473, Indianapolis, IN 46202-5289

^E-mail:ude.iupni@nrohniel.

Contributed by Lawrence H. Einhorn

Accepted 2002 Feb 5.

Abstract

Our initial studies with cisplatin + vinblastine + bleomycin began 27 years ago in 1974, changing the cure rate for disseminated disease from 5 to 60%. Subsequently, through random prospective clinical trials, we have modified the treatment regimen to reduce both the duration and dosages of the chemotherapy drugs. Cisplatin + etoposide was first used at Indiana University as salvage chemotherapy in 1978, representing the first time that a solid tumor had been cured with second-line chemotherapy. We next did a clinical trial comparing bleomycin + etoposide + cisplatin (BEP) to cisplatin + vinblastine + bleomycin. The BEP regimen was proven to have less toxicity and a higher cure rate and therefore, since 1984, has been standard chemotherapy. More recent studies have evaluated the use of lesser chemotherapy to maintain the same cure rate for patients with good-prognosis disease. Standard therapy for these patients is either three courses of BEP or four courses of EP, and over 90% of these patients will be cured of their disease. Patients who are not cured with their initial BEP chemotherapy are usually treated with salvage chemotherapy. Approximately 50% of these testicular cancer patients will subsequently be cured with salvage chemotherapy with tandem transplant of high-dose chemotherapy with peripheral stem cell rescue. Testicular cancer has become a model for a curable neoplasm. In the early 1970s, metastatic testicular cancer was associated with only 5% survival. Today, with modern chemotherapy and surgery techniques, 80% of patients will survive their disease.

Abstract

Germ cell tumors are relatively uncommon, accounting for only 1% of male malignancies in the United States. The highest worldwide incidence is in Scandinavian countries; by contrast, testicular cancer is rare in African Americans. The primary age group is 15–35 for nonseminomatous tumors and a decade older for seminoma.

In 2001, there were ≈8,000 newly diagnosed cases in the United States, contrasting sharply with the 190,000 cases of prostate cancer, the most common male malignancy.

Despite the paucity of cases, this tumor has become an extremely important oncological disease. First, it is the most common carcinoma in young men ages 15–35 and thus has the potential to greatly shorten productive years of life. Second, available serum markers (alphafetoprotein and human chorionic gonadotropin) allow the clinician to make important and accurate treatment-related decisions. Third, testicular cancer has been a model for multidisciplinary care, as surgical resection of postchemotherapy radiographically persistent disease can improve the cure rate. Fourth, germ cell tumors have become an excellent testing ground for active experimental drugs (e.g., cisplatin, etoposide, and ifosfamide, all of which were approved by the Food and Drug Administration primarily on the basis of data in testicular cancer). The goal of chemotherapy in germ cell tumors is never merely palliation or prolongation of survival, but cure.

Abbreviations

PVB	cisplatin + vinblastine + bleomycin
BEP	etoposide + bleomycin
NED	no evidence of disease

Abbreviations

Footnotes

This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected on May 1, 2001.

^{PVB: cisplatin, 20 mg/m}^{days 1 to 5; vinblastine, 0.2 mg/kg, days 1–2; bleomycin, 30 units, days 2, 9, and 16. (}i) Courses were repeated every 3 weeks for four courses; (ii) after PVB induction, single-agent maintenance vinblastine (0.3 mg/kg) every 4 weeks was utilized for a total of 24 mo of chemotherapy.

Footnotes

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