Why is cisplatin a very potent antineoplastic for testicular cancer, but not necessarily for other cancers?

Question

Cisplatin (structure below) is a platinum-based chemotherapeutic agent which is very effective in the treatment of some cancers. Its introduction was responsible for improving the cure rate for testicular cancer from 10% to 85% according to the wikipedia page on cisplatin.

However, it is not very effective for other types of cancers; interestingly, ovarian cancer does not respond well to it (Siddick, 2003).

Does someone know why cisplatin is so specific to testicular cancer? I haven't found any sources explaining this.

Answer 1

From the dedicated cisplatin website and Drugbank it appears its use is quite diverse and not confined to testicular cancers. Further, your linked (Siddick, 2003) paper mentions on the first line of its abstract that cisplatin has clinical activity against a wide variety of solid tumors.

Cisplatin.org mentions that cisplatin finds use as chemotherapy against a range of cancers:

Cisplatin is a chemotherapy drug which is used to treat cancers including: sarcoma, small cell lung cancer, germ cell tumors, lymphoma, and ovarian cancer. [I]t can be a valuable part of a combination chemotherapy regimen. Look at the regimens given to patients and you will often see cisplatin as one of the drugs.

Moreover, cisplatin is explicitly used to treat ovarian cancer:

Treatment of ovarian cancer involves putting the cisplatin into the peritoneal cavity rather than a blood vessel. The type and extent of a cancer determines the exact dose and schedule of administering the drug.

As to your comment that cisplatin has "magical powers" I can say that it does not. The article that your linked cisplatin wikipedia page refers to (Einhorn, 1990) is a review paper that describes the efficacy of combination therapies with cisplatin. The high cure rate of 75% was reached when cisplatin was used in combination with etoposide plus bleomycin. The last 10% was theorized to be achievable with 'salvage chemotherapy'. Hence, it is not cisplatin on its own.

In general, it is common practice to use various chemotherapeutic agents in consort, preferably with differing modes of action to reduce the dose of each and hence lessening the side effects.

References
- Einhorn, JCO (1990); 8(11): 1777-81
- Siddick, Oncogene (2003); 22: 7265–79

Answer 2

Any apparently "magical" powers of cisplatin in testicular cancer have more to do with the disease than the drug.

Unlike the similarly male-specific prostate cancer, testicular cancer is generally seen in young men in their 20s or 30s (click on "number of new cases and deaths"). This paper suggests, as is generally thought to be the case for earlier-onset types of cancer, that the affected individuals thus had some predisposing mutation or change in gene regulation prior to 10 years of age. As a result, it takes fewer sporadic acquired mutations to lead to this early-onset cancer versus a late-onset type like prostate.

This difference in incidence pattern is important because a late-onset tumor has had more opportunity to develop a broad range of cancer cells having different mutations within the tumor. Such intra-tumor heterogeneity has been recognized for over 30 years as a reason for resistance of tumors to cell-killing therapy like chemotherapy. For example, a heterogeneous tumor might be more likely to have cells that have mutated in a way that happens to make them resistant to cisplatin.

Also, testicular cancers develop in an accessible part of the anatomy that typically receives a lot of attention from men of the ages of peak incidence, so they are much more likely to be caught at an early stage than are prostate, ovarian, or colon cancers within the abdomen.