Risk Stratification, Clinical Management, and Late Complications of Chemotherapy for Testicular Cancer

Risk Stratification, Clinical Management, and Late Complications of Chemotherapy for Testicular Cancer

Dr. Lawrence H. Einhorn, credit Zach Hetrick
Lawrence H. Einhorn, MD, FASCO, distinguished professor of medicine at the Indiana University School of Medicine, will discuss management of clinical stage I disease, risk stratification, and chemotherapy for testicular cancer during his keynote lecture on February 17. He will also provide important insights about salvage therapy for patients not cured with initial chemotherapy and will discuss late complications of platinum-based chemotherapy.

Dr. Einhorn is best known for his contribution to one of the greatest achievements in the field of oncology: the introduction of platinum combination therapy for testicular cancer in 1974. His pioneering research on cisplatin resulted in the discovery of an effective cure for testicular cancer that, previously, almost always had fatal outcomes; prior to Dr. Einhorn’s breakthrough discovery, approximately 90% of patients with metastatic testicular cancer died within 1 year.1

Since the first introduction of platinum combination therapy more than 40 years ago, platinum agents have been successfully used as first-line therapy in 12 different malignancies, transforming the oncology field. Dr. Einhorn spent the next few decades refining the treatment of testicular cancer—minimizing treatment toxicity and increasing therapeutic efficacy. In phase III studies, his team demonstrated that reducing the dosage of vinblastine resulted in reduced neuromuscular and hematologic toxicity, eliminating the need for 2 years of maintenance vinblastine. His research also demonstrated that substituting etoposide for vinblastine yields higher cure rates and lower toxicity.

Genomic Susceptibility to Platinum-Based Chemotherapy Complications

In an interview with the Genitourinary Cancers Symposium Daily News, Dr. Einhorn said that 95% of all patients diagnosed with testicular cancer in 2016 will be cured, which includes 80% of patients with metastatic disease.

“These latter patients will either be cured with initial chemotherapy or subsequent salvage therapy, which sometimes can include salvage surgery rather than salvage chemotherapy,” he said. “Salvage chemotherapy with ifosfamide-based chemotherapy or high-dose chemotherapy in peripheral blood stem cell transplant allows realistic probability for cure in [patients with] refractory [disease].”

An 80% cure rate for metastatic testicular cancer is substantially higher than the cure rate for any other metastatic disease treated with chemotherapy. Because it would be difficult to improve upon these results, Dr. Einhorn’s present research focus is on reducing toxicity and determining genetic susceptibility to late complications of platinum-based chemotherapy.

In the scope of earlier clinical trials, Dr. Einhorn’s team was already successful in mitigating severe chemotherapy-induced nausea and vomiting through an improved use of antiemetics. Other common side effects of treatment with platinum-based chemotherapy include neuropathy, hearing loss, and heart disease. Presently, Dr. Einhorn’s North American collaborators are investigating strategies to alleviate these remaining burdensome side effects.

One of Dr. Einhorn’s current research projects, which was funded by a National Cancer Institute RO1 grant, involves following patients who were younger than age 55 at the time of starting platinum combination chemotherapy, who were therapy free for more than 1 year, and who have not required salvage chemotherapy.

“We are specifically looking at neurotoxicity and ototoxicity and already have uncovered genomic markers for these chronic problems,” he said. “We hope to also evaluate cardiovascular and secondary malignancies and look at genomic understanding of this as well.”

Looking Ahead: Molecular-Targeted Therapy

In an interview with the Genitourinary Cancers Symposium Daily News, Dr. Einhorn reflected on the current trends and future prospects in testicular cancer research.

“Testicular cancer is a unique disease, as the advances with metastatic disease have entirely been [because of] the chemotherapy,” he said. “However, we have probably gone as far as we can go with chemotherapy in epithelial malignancies. The future, as well as the present, involves finding the molecular drivers of tumors in looking for molecular-targeted therapy.”

Dr. Einhorn said that this holds true for many other malignancies, including lung cancer, where the discovery of EGFR, ALK, and ROS1 mutations sparked research focused on developing new therapies targeting these mutations. He also noted that immunotherapy with immune checkpoint inhibitors looks promising in other malignancies as well; it is well tolerated and has proven to have a wide field of applicability. Immune checkpoint inhibitors have already been used in treatment of several types of cancer including non–small cell lung cancer, melanoma, kidney cancer, and Hodgkin lymphoma. However, Dr. Einhorn noted that we are still early in the process of learning the optimal timing and duration for immunotherapy treatment, as well as how to combine immune checkpoint inhibitors with other therapeutic agents. 

–Jasenka Piljac Žegarac, PhD