Platinum Study Q&A

Lessening the burden on cancer survivors

The American Society of Clinical Oncologists rates cisplatin among its top five cancer research breakthroughs. 

But that’s not good enough for Dr. Larry Einhorn, the pioneer who developed the treatment in the 1970s. He believes the side-effect tradeoff is unacceptable.

Today, Einhorn and internationally-renowned cancer survivorship expert Dr. Lois Travis are leading a long-term study focused on lessening the burden cisplatin-based therapy puts on patients.

The Platinum Study is a longitudinal research study designed to gain new information that can benefit future testicular cancer patients. We're looking at the long—term health of men who have been treated for a specific type of cancer with cisplatin chemotherapy.

Our initial aim of this study was to establish a well-characterized cohort for lifelong follow-up to study the genetics of long-term side effects. Specifically, we want to identify any genetics associated with long- term neurotoxicity (numbing/tingling in the hands and/or feet) and ototoxicity (hearing loss).

By looking at participants' health background and basic measurements, we’re now using this information as baseline data for studies of genetic risk of other long-term toxicities, such as cardiovascular disease.

What we’re learning will help millions of patients around the world.

Lois B. Travis, MD, ScD — Principal Investigator

While 95 percent of testis cancer patients are cured, the combination of cisplatin and other drugs that saves them can leave behind lingering side effects. These include hearing loss, pain and numbness in extremities, a higher risk for other cancers, and even cardiovascular disease.

Ultimately, we hope this research can determine which patients are most likely to experience adverse effects from cisplatin, and then provide guidelines that could decrease damaging side effects, such as duration of treatments or improved symptom management.

When Dr. Lawrence Einhorn joined the faculty of IU School of Medicine in 1973, testicular cancer was the leading cause of cancer death among men between the ages of 15 to 35. When surgery failed, these young men turned to Dr. Einhorn to treat the spread of the disease.

Einhorn developed a revolutionary therapy, using a regimen of platinum-based cisplatin and two other drugs. His pioneering work flipped the 95 percent mortality rate for the disease to a 95 percent survival rate—and it's still the only cure discovered for metastasis of a solid tumor.

In our preliminary research, we collected information about participants' health, with a short list of questions, some basic measurements like blood pressure, a blood sample to be used only for research purposes, and a hearing test.

The baseline results from audiometric testing surprised us:

  • 80 percent of the patients had hearing loss with one in five classified as severe to profound, levels at which hearing aids are recommended
  • 56 percent of patients had nerve damage called neuropathy
  • 40 percent had tinnitus or permanent ringing in their ears

We found that a mutation in a specific gene was related to hearing loss and this showed a significant interaction with cisplatin dose, thus having potential clinical impact to predict susceptibility.

In addition, we found that 38 percent of the survivors at a young median age of 37 years already had more than three adverse health outcomes. These included everything from hypertension to diabetes to cardiovascular disease and more.

This is concerning since these men are young at diagnosis, have an overall 97 percent five-year survival rate, and could live upwards of 50 years or more.

Meet the Investigators: Chunkit Fung, MD

University of Rochester, New York

Dr. Fung specializes in genitourinary malignancy with clinical research interests in cancer control to prevent and manage treatment-related toxicities and cardiovascular complications in cancer survivors. Additionally, he is interested in developing clinical trials for genitourinary cancers to evaluate new therapies.

We're continuing to follow health changes, especially those associated with age-related hearing loss. We're concerned with the social and emotional consequences of the constant ringing in the ears, such as difficulty sleeping or concentrating.

Other ongoing research includes:

  • Tracking pain and numbness associated with neuropathy, as well as other toxicities.
  • Monitoring patient blood samples for platinum levels, which can remain in the body for decades after chemotherapy is completed.
  • Finding new biomarkers to help monitor the effects of chemotherapy or other kinds of treatment.
  • Learning how genes interact with other factors, like the environment or personal habits such as exercise or smoking, and how they may influence the development of diseases such as heart disease or nerve damage.

More than 2,000 testicular cancer survivors are part of the largest clinical cohort of germ cell cancer survivors worldwide.

Testicular cancer survivors were chosen to study cisplatin-related toxicities because of their young age at diagnosis, homogeneity of cisplatin-based therapy (usually either cisplatin, etoposide and bleomycin), high cure rate (overall 97 percent five-year survival) followed by upwards of 50 years of survival, and eventual opportunities for intervention.

Eligibility criteria included:

  • Male, 18 years of age or older at time of consent
  • Diagnosed at age 60 or younger
  • Proficient in English
  • Diagnosis or confirmation of diagnosis of a histologically or serologically confirmed germ cell tumor (or extragonadal germ cell tumor) by one of the participating sites
  • Treatment consisted of cisplatin-based chemotherapy regimen for either initial or subsequent germ cell tumor
  • Subject completed chemotherapy ≥ 6 months ago (at time of consent)
  • Subject did not require salvage chemotherapy treatment or bone marrow transplant
  • Subject had no prior chemotherapy for a different cancer

Testicular cancer survivors are instrumental to learning about the long-term trajectory of cisplatin-related toxicities, and well as the underlying genetic underpinnings. Both of these facets of our research will be applied to the many other patients worldwide who receive cisplatin-based chemotherapy.

The study was initially funded by the National Cancer Institute in the United States. The success of this research led to the NCI awarding Dr. Travis an additional five-year, $5.7 million grant to continue following all participants.


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