Current Trends in Chemotherapy for Metastatic Nonseminomatous Testicular Germ Cell Tumors

Abstract

With the introduction of cisplatin-based chemotherapy, metastatic testicular cancer represents a model for a highly curable malignant disease. Approximately 70–80% of patients achieve a durable remission following chemotherapy ± secondary surgery of residual tumors. With the development of prognostic classifications based on clinically available parameters, the aims of chemotherapy have been twofold: on the one hand, the reduction of toxicity in patients with ‘low-risk’ metastatic disease without a concomitant reduction in treatment efficacy and, on the other hand, the improvement of treatment results in patients with ‘poor-prognosis’ criteria who achieve a long-term cure rate of less than 50% with standard chemotherapy regimens. Despite a number of large randomized studies attempting either to avoid the toxicity of bleomycin or to reduce cisplatin-associated side-effects through the substitution with carboplatin, the combination of cisplatin, etoposide and bleomycin (PEB) given at 3-week intervals still remains the standard treatment for metastatic disease. The role of high-dose chemotherapy with autologous stem cell support is currently being investigated in order to improve the outcome of patients with relapse after previous chemotherapy and of patients initially exhibiting advanced metastatic disease. For patients with relapsed disease receiving high-dose chemotherapy, a prognostic score has recently been developed: cisplatin-refractory disease, beta human gonadotropin values >1,000 U/l or primary mediastinal germ cell tumors are factors characterizing patients which will profit less from high-dose chemotherapy treatment than patients with chemosensitive disease at relapse. Standard dose salvage regimens only result in a 20% long-term survival rate. In contrast, high-dose salvage chemotherapy may yield a cure rate of approximately 40%. However, the only randomized study comparing high-dose versus conventional-dose therapy in patients with relapsed disease is still ongoing. The investigation of dose-intensive approaches as first-line treatment is currently being studied by several institutions. Despite preliminary favorable results, this approach still cannot be considered standard treatment. A randomized study comparing high-dose chemotherapy with 4 cycles of standard PEB was initiated in the USA in 1996. The evaluation of new drugs in testicular cancer patients with absolute cisplatin-refractory disease has demonstrated that paclitaxel is one of the few agents with antitumor activity in these patients. Paclitaxel has therefore been included in combination regimens – such as cisplatin, ifosfamide and paclitaxel – for the treatment of patients with first and second relapse of testicular cancer. These combinations are used as induction therapy prior to high-dose salvage treatment. Due to the large group of patients with metastatic disease being cured nowadays, the long-term side effects of treatment have become even more important. One of the major risk factors for the development of late toxicities such as ot...

Treatment-induced anaemia and its potential clinical impact in patients receiving sequential high dose chemotherapy for metastatic testicular cancer

“…With the higher number of transfusions given, the potential side effects of RBC transfusions, such as viral infections, haemolysis, immunological or anaphylactic reactions may contribute to the risk associated with the treatment in this young patient population (Groopman and Itri, 1999;Mercadante et al, 2000). This is of particular importance, since between 50% and 80% of all patients will be cured from testicular cancer by this dose intensified treatment approach (Bokemeyer et al, 1998;Sonneveld et al, 2001). With a median of 10 RBC units transfused to each patient, the impact of cisplatin-based sequential high dose chemotherapy on erythropoiesis and the importance of therapyinduced anaemia is clearly demonstrated.…”

“…With the use of cisplatin-based combination chemotherapy, 70 -90% of the patients with metastatic testicular cancer will be cured (Bokemeyer et al, 1998;Hartmann et al, 1999). However, in patients fulfilling 'poor prognosis'-criteria according to the IGCCCG classification the actual 5-year survival rate is only 50 -60% (IGCCCG, 1997;Sonneveld et al, 2001).…”

Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer

“…Because of the excellent long-term prognosis of patients with this type of solid tumour (Bokemeyer, 1997;Bosl and Motzer, 1997), it was possible to study the subjective and objective quality-of-hearing impairment in an almost healthy patient cohort with emphasis on long-term ototoxicity after a minimum follow-up period of …”

“…Because of the excellent long-term prognosis of patients with this type of solid tumour (Bokemeyer, 1997;Bosl and Motzer, 1997), it was possible to study the subjective and objective quality-of-hearing impairment in an almost healthy patient cohort with emphasis on long-term ototoxicity after a minimum follow-up period of MATERIALS AND METHODS Patients In this study, 182 patients treated for testicular cancer between 1976 and 1987 and followed through the oncological outpatients clinic at Hannover University Medical School were invited to be interviewed and examined concerning the detection of possible late toxicities after chemotherapy. The evaluation of ototoxicity was part of an extensive screening programme concerned with identifying prevalence, relevance and risk factors for different organ toxicities, such as neurotoxicity, vascular toxicity, gonadal toxicity and other chemotherapy-induced alterations of body functions (Bokemeyer et al, 1996).…”

The role of high-dose chemotherapy in the treatment of testicular cancer

“…[5][6][7] Such results have provided the theoretical background for the use of HDC in testicular cancer. HDC initially with autologous bone marrow and then with HSCT has been used for nearly two decades and has shown high response rates and promising disease-free rates in poor risk patients (prior to the establishment of the IGCCCG criteria) in predominantly noncontrolled trials.…”