Cisplatin is a platinum-based chemotherapy drug used to treat several types of cancer, most notably testicular cancer, ovarian cancer, and bladder cancer. It works by damaging the DNA inside cancer cells, preventing them from dividing and ultimately triggering cell death. First approved decades ago, it remains one of the most effective chemotherapy agents available and is still a cornerstone of treatment for certain cancers.
Cancers Treated With Cisplatin
Cisplatin has three primary approved uses. It treats advanced testicular cancer (typically combined with other drugs after surgery or radiation), advanced ovarian cancer that has spread beyond the ovaries, and advanced bladder cancer when other therapies like surgery or radiation aren’t viable options. For bladder and testicular cancers in particular, cisplatin-based regimens are considered the gold standard rather than just one option among many.
Beyond these approved indications, cisplatin is widely used in clinical practice for lung cancer, head and neck cancers, cervical cancer, and certain pediatric solid tumors like neuroblastoma. In these cases, oncologists use it based on strong clinical evidence even though it may not carry a specific label approval for each cancer type.
How Cisplatin Kills Cancer Cells
Once cisplatin enters a cell, it undergoes a chemical change that allows the platinum atom at its core to bind directly to DNA. It latches onto neighboring building blocks of the genetic code, particularly guanine bases, forming what scientists call “crosslinks.” About 65% of the damage involves two adjacent guanine bases being locked together, with another 25% involving a guanine-adenine pair. These crosslinks physically distort the DNA strand, like kinking a garden hose.
When a cell detects this kind of severe DNA damage, it can no longer copy its genetic material accurately. The cell’s repair systems attempt to fix the problem, but if the damage is too extensive, built-in safety mechanisms trigger programmed cell death. This is what makes cisplatin effective: it overwhelms cancer cells’ ability to repair themselves.
Testicular Cancer: A Remarkable Success Story
Cisplatin’s impact on testicular cancer is one of the most dramatic success stories in oncology. Modern cisplatin-based chemotherapy cures more than 95% of patients with testicular cancer, even when the disease has spread. Before cisplatin was introduced in the late 1970s, metastatic testicular cancer was frequently fatal. The drug transformed it into one of the most curable cancers in medicine.
Treatment typically involves cisplatin combined with other chemotherapy drugs, given in cycles after surgery. Most young men who complete treatment go on to live full lives, though researchers continue to study the long-term health effects that can emerge years or decades after treatment.
Bladder Cancer and Presurgical Treatment
For muscle-invasive bladder cancer, cisplatin is frequently given before surgery, an approach called neoadjuvant chemotherapy. The goal is to shrink the tumor before the bladder is removed, improving the odds of a complete cure. A large meta-analysis found that giving cisplatin-based chemotherapy before surgery reduced the risk of death by about 20%, translating to roughly 76 fewer deaths per 1,000 patients compared to surgery alone. That’s a meaningful survival advantage, which is why guidelines strongly recommend it for patients healthy enough to tolerate the treatment.
Ovarian Cancer Combinations
In advanced ovarian cancer, cisplatin is one of several platinum-based drugs used after surgical removal of as much tumor as possible. It’s often paired with a drug that disrupts cell division through a different mechanism, and treatment typically runs for three to nine cycles depending on the specific regimen and how the cancer responds. Carboplatin, a newer platinum drug, has largely replaced cisplatin as the default choice in ovarian cancer because it causes fewer side effects, though cisplatin remains an option in certain protocols, including regimens where chemotherapy is delivered directly into the abdominal cavity.
Side Effects and Organ Damage
Cisplatin is effective, but it’s also one of the more toxic chemotherapy drugs. Its side effects can be severe enough to limit how much treatment a person can receive.
Hearing Loss
Cisplatin damages the delicate hair cells in the inner ear that convert sound waves into nerve signals. An estimated 36% of adults and 40% to 60% of children treated with cisplatin develop some degree of hearing loss. Receiving cisplatin increases the risk of hearing impairment fivefold. The damage tends to affect high-frequency sounds first and is generally permanent. For children, this can interfere with speech and language development, making monitoring especially important in pediatric patients.
Kidney Damage
The kidneys are particularly vulnerable to cisplatin because they concentrate the drug as they filter blood. Kidney damage is common enough that patients receive large volumes of intravenous fluids before and after each treatment to help flush the drug through the kidneys and reduce exposure. Kidney function is monitored closely throughout treatment, and doses may be adjusted or treatment switched to a different drug if kidney function declines significantly.
Nerve Damage
Cisplatin can cause peripheral neuropathy, a tingling, numbness, or pain in the hands and feet that results from damage to sensory nerves. This side effect tends to worsen with cumulative doses and may not fully resolve after treatment ends.
Nausea and Vomiting
Cisplatin is one of the most nausea-inducing chemotherapy drugs. Modern anti-nausea medications have dramatically improved this, but patients should expect to receive a multi-drug anti-nausea regimen with each treatment cycle.
Cisplatin vs. Carboplatin
Carboplatin was developed specifically to retain cisplatin’s cancer-killing ability while reducing its harshest side effects. In many cancers, the two drugs perform similarly. A meta-analysis of non-small cell lung cancer trials found no significant difference in overall survival between cisplatin and carboplatin regimens, though cisplatin showed a small advantage in tumor shrinkage rates.
The side effect profiles differ in meaningful ways. Cisplatin causes more nausea, vomiting, kidney damage, nerve damage, and hearing loss. Carboplatin is more likely to lower blood cell counts, causing anemia and increasing bleeding risk. Because of these differences, carboplatin has become the more commonly used platinum drug in the United States, where fewer than 10% of oncologists prescribing platinum-based regimens choose cisplatin. In Europe, guidelines have historically favored cisplatin for patients healthy enough to tolerate it, particularly when maximum tumor shrinkage is the priority.
The choice between the two drugs depends on the specific cancer, the treatment goal, and the patient’s overall health. Cisplatin remains the preferred option in testicular cancer and in certain bladder cancer protocols where it has the strongest evidence base. For ovarian and lung cancers, carboplatin has become the more common default.
Why Cisplatin Sometimes Stops Working
Some tumors are resistant to cisplatin from the start, and others develop resistance during treatment. This happens through several mechanisms working simultaneously. Cancer cells can reduce the amount of drug they absorb, increase the rate at which they pump the drug back out, or neutralize the drug with sulfur-containing molecules before it reaches the DNA. Perhaps most importantly, cancer cells can become better at repairing the DNA damage cisplatin causes, using a process called nucleotide excision repair to snip out and replace the damaged sections of their genetic code. Because resistance involves multiple overlapping strategies, it’s difficult to overcome with a single approach, which is one reason cisplatin is almost always used in combination with other drugs.