Metastatic Germ-Cell Tumors Potentially Curable With High-Dose Chemotherapy

July 27, 2007 — The administration of high-dose chemotherapy plus hematopoietic stem-cell rescue can potentially provide a cure for testicular cancer, even when used as a third-line option or in patients with disease that is platinum refractory. This finding is reported in a retrospective review in the July 26 issue of the New England Journal of Medicine.
"Testis cancer is unique," lead investigator Lawrence E. Einhorn, MD, a distinguished professor and Lance Armstrong Foundation professor of oncology at Indiana University School of Medicine in Indianapolis, told Medscape. "There are few if any other types of cancer in which there is any realistic chance for cure after failing to be cured with prior chemotherapy."
Cisplatin-based chemotherapy has been shown to be curative in 79% of patients with newly diagnosed metastatic germ-cell cancers, but it is less well-established what factors are associated with long-term survival following salvage therapy. Candidates for salvage therapy are those with tumors that progress despite initial treatment or who relapse. In this study, the goal of the researchers was to examine the efficacy of high-dose carboplatin plus etoposide plus rescue hematopoietic peripheral blood stem-cell rescue, in patients with cisplatin-resistant, progressively growing testicular cancer.
Dr. Einhorn and colleagues reviewed the cases of 184 patients with metastatic testicular cancer whose disease had progressed despite treatment with cisplatin-containing combination chemotherapy. The patients had all received high-dose chemotherapy and peripheral blood stem-cell rescue between February 1996 and December 2004. The regimen consisted of 700 mg of carboplatin per square meter of body surface area plus 750 mg of etoposide per square meter, which were administered 5, 4, and 3 days prior to an infusion of stem cells.
"High dose chemo is our first option for patients who fail to be cured with standard dose chemotherapy," Dr. Einhorn told Medscape. "Some centers will instead use standard dose platinum combination chemotherapy with cisplatin plus ifosfamide, and either vinblastine or paclitaxel and reserve high dose chemo, if needed, for 3rd line chemotherapy."
At a median follow-up of 48 months, 116 (63%) of the cohort had remained continuously free of disease. Of this group, 104 (90%) were disease free for more than 2 years. A complete remission was observed in 6 additional patients; 4 patients experienced a remission after receiving paclitaxel plus gemcitabine, and 2 patients had a remission after they underwent a subsequent germ-cell tumor resection.
The researchers found that certain variables were significantly associated with progression-free survival. These included the use of high-dose chemotherapy as a second-line agent as compared with third-line chemotherapy, the tumor response to cisplatin, the response to initial chemotherapy, a favorable International Germ Cell Cancer Collaborative Group (IGGCCG) score, and favorable prognostic features.
A further breakdown of survival showed that of the 61 patients with favorable prognostic features, 49 experienced a continuous period of remission for a median of 46 months. In the subgroup of 40 patients with progressive metastatic disease and platinum-refractory tumors, 18 remained disease free for a median of 49 months.
Grade 3 or higher toxic adverse effects developed in 55 patients following high-dose chemotherapy. The most common were gastrointestinal related, but 3 patients developed leukemia with 2 subsequent deaths. Three other patients experienced sudden drug-related deaths, in which 2 were caused by hepatic failure and the third from toxic pulmonary effects.
"The key point of this study is that even after going through a difficult course of initial chemotherapy and experiencing a relapse of the cancer, there is still a high probability for a cure with salvage chemotherapy using high dose chemotherapy," said Dr. Einhorn. "Our other key point is that is was possible to overcome drug resistance to standard doses of platinum plus etoposide with high dose chemo, as 18 of 40 of patients who progressed within 4 weeks of their last course of standard dose chemotherapy were cured with high dose chemotherapy."
N Engl J Med. 2007;357:340-348.