The chemotherapy protocols used for testicular cancer vary from country to country and even from hospital to hospital. That makes life a little more complicated, but in general, there are two accepted chemotherapy protocols for good risk testicular cancer: Either 3 cycles of BEP (Bleomycin, Etoposide, and Cisplatin) or 4 cycles of EP (Etoposide and Cisplatin). The standard protocols used in the US call for the cisplatin and etoposide to be given, inpatient or outpatient, over a period of 5 days. Some other countries and some experimenters in the US have tried to give the chemo over a period of 1-3 days, but in my opinion, they are really trying to save money more than they are trying to benefit the patient. Also, in Europe they tend to use less Etoposide per cycle.

For intermediate and poor risk germ cell tumors, the standard protocol is 4 cycles of BEP. Some institutions use a protocol called VIP (Etoposide, Ifosfamide, and Cisplatin) and/or use high dose chemo with a stem cell transplant (Carboplatin and Etoposide) to treat poor risk patients. Typically, the stem cell transplant is not used outside of a clinical trial.

Please note that Carboplatin, while related to Cisplatin, is not as effective as Cisplatin. It should never be used to treat nonseminomatous germ cell tumors except during a stem cell transplant.

The two protocols (EP and BEP) are essentially identical in terms of cure rate. They are different in terms of length and possible side effects. The BEP protocol uses less Cisplatin and Etoposide, but uses Bleomycin. Bleomycin can cause lung fibrosis in older patients (over fifty) and can be a problem in patients with extensive lung metastases or existing lung problems. Etoposide can cause leukemia many years down the road (at the levels given during standard chemo, the risk is less than 1 percent.) and Cisplatin can cause neuropathy and hearing loss, so there is some impetus to reduce the number of cycles of these drugs. Which should YOU choose? Well, you usually won't be asked. These protocols typically vary from hospital to hospital. Memorial Sloan Kettering strongly prefers EP while Indiana University prefers BEP. If you have any concerns, please discuss them with your doctor before starting chemotherapy...

John S, one of the TC survivors on our email support list, did some research into the bleomycin question. He asked a couple of doctors about problems associated with oxygen exposure. He learned that the more Bleo you receive, the greater the risk of this pulmonary toxicity. Most doctors don't worry too much about this side effect until you're up in the 300-400 units range. His doctor recommended a MedicAlert bracelet for a year or two just in case you're knocked unconscious and they decide to put you on oxygen. However, he said that if it's life-threatening situation, it's best to get the oxygen. Ditto for oxygen masks on an airplane. If they drop down, put them on.

The other question he had concerned scuba diving. After all, you're not breathing concentrated oxygen, just compressed oxygen. He consulted with Daniel A. Nord from the DAN Medical Staff. DAN (Diver's Alert Network) is an organization dedicated to dive safety and medical issues. Daniel wrote back explaining that, "Bleomycin is a cytotoxic drug of particular importance to divers as it causes pulmonary toxicity in generally 4% of patients, usually in the form of pneumonitis/fibrosis. Even in patients with no obvious pulmonary toxicity, the lungs are sensitized to raised levels of inspired oxygen, causing an adult respiratory distress syndrome. In general, anyone who has had bleomycin should not be exposed to partial pressures of oxygen greater than 0.3 ata's, approx. 15 feet salt water on normoxic air. Sorry to have to advise that from a medical perspective, diving is not recommended. If you would like to discuss this in further detail, please feel free to contact this office directly at (919) 684-2948."

We asked Dr Nichols about the issues associated with bleomycin. He told us, "that patients who received bleomycin should always make sure that, now and forever, their doctors and anesthesiologists should be reminded about this before any surgery or sedation. I suspect the risk of O₂ toxicity declines over time, but as far as I know this is unknown. I don't think any additional information need be related to medical personnel and always, if oxygen is required in a life threatening emergency (eg heart attack or respiratory arrest etc.) it should be given." We have also asked Dr Lawrence Einhorn at Indiana University about the same thing, and his position is that the a good part of bleomycin toxicity issue is overstated and the negative aura has grown over time without any medical evidence.

So there you have it: Put on the mask, sell your respirator and tanks, and buy a medical alert bracelet or necklace! Or not... Keep your eyes open. I hope to give this issue more space in the near future.

Salvage Chemotherapy

Salvage chemo. It doesn't have a nice ring to it, does it? Well, truth be told, not everyone with testicular cancer is going to be cured by the first attempt at chemotherapy. But just because the first chemo fails to cure does not mean that all is lost. Depending on the type and timing of the recurrence, many patients can still be cured of their disease.

No matter when the recurrence, be it 1 month or 10 years after chemotherapy is finished, I strongly recommend that the patient's doctor contact one of the experts on our experts list to learn about the proper way to treat the problem. There is a lot of research in this area, and new treatments are being tried all of the time. Be aware that more than one study has determined that getting treated by an expert will improve your chances for survival. The experts know what they are doing and are willing to share this information. Please make use of them. The articles and links listed below also have some good information.

This may sound stupid, but it is very important that salvage therapy is not given unless a relapse is clearly occurring and is documented by a biopsy or a clearly rising and significant levels of markers. It is not that rare for patients to be mistakenly classified as having recurrent disease based on false-positive markers or abnormal x-ray results. Some of these false-positive results may be due to a growing teratoma (which still would require surgery), pseudonodules from bleomycin-induced pulmonary disease, or elevated markers from other causes such as elevated b-HCG from marijuana usage or cross-reactivity with luteinizing hormone, or elevated AFP associated with hepatitis or liver dysfunction. Tests can and should be done to ensure that a slightly positive marker level is really due to cancer and not something else! Another cause of persistently elevated markers is a tumor sanctuary site (eg, in the testis or brain). Now, this is still cancer, but it may be treated differently than recurrent cancer in the abdomen.

Most salvage chemotherapy for testicular cancer is VeIP with or without high dose therapy, and this protocol results in 30-50% of patients being cured assuming that they are not cisplatin refractory. During this type of therapy, it is generally routine to prescribe G-CSF. Be aware that chemo may not be a solution, so it is important that you explore surgical options as well.

A Few Important Final Tips

Chemotherapy is a complicated subject. The drugs used can make you sick, typically much sicker than you felt from the cancer alone. There are many different drugs used and many different ways to use those drugs. Oncology may seem like a cookie cutter / recipe driven way to cure cancer, but it is not. Experience does count, and if your doctor does not have a lot of experience with testicular cancer, you might want to ask them review your treatment with their peers and with an expert.

Over the years, we have learned a few things about the administration of chemotherapy for testicular cancer. Discuss this information with your doctor, and make sure that both of you agree how to deal with these issues before starting chemo.

• Delays During Chemotherapy

  Chemotherapy usually has some effect on the immune system. With many chemotherapy protocols, it is not unusual for the oncologist to delay a cycle if a patients white count is below a certain level. This is not the case with testicular cancer. If a patient is receiving BEP, EP, or VIP, each cycle and dose of chemo should be given on schedule regardless of the white count!

  For example, a patient wrote, "I was supposed to get my dose of Bleomycin today, but my white blood cell count had dropped too low. The doc is now recommending both abstaining from the bleo, and waiting an extra week to begin my next cycle in order to let the count come back up. I consulted with another Oncologist -- mine wouldn't return my calls. This other doc said that, given how low my white cell count is, he'd (pretty strongly) recommend Neupogen to boost the count."

  Dr Nichols' response was, "The Bleo should be given since it doesn't really effect the white count. We always give Bleo irrespective of the white blood cell count. We don't usually add neupogen at this point since it takes several days to work, and he already is starting to recover. His next cycle should be initiated as planned irrespective of the white count. Patients are almost always recovering at that point."

  I later asked Dr Nichols specifically, "Under what circumstances would you postpone the start of the next BEP cycle? Would your answer change if the protocol was VIP?" He says that, "The correct answer is very rarely for any circumstances related to myelosuppression. What we do is start virtually everyone on the correct day and watch their counts over the 5 days. If, and this is very uncommon, the white count doesn't start to rise we hold the last day of etoposide. Most everyone has a rising white count at that juncture. There is little to no evidence that holding chemotherapy until the white count reaches an arbitrary number is safer."

  Finally, I asked him about the consequences of delaying a cycle. He told me that, "There is published data that delaying a cycle by more than 7 days does worsen the results. There is also data that a lower cisplatin dose intensity, measured in mg/m2/week, does worse. The standard EP dose intensity is 33 mg/m2/wk and we know that 20/mg/m2/week is worse. No one knows whether a 3 day delay is harmful, but it certainly is inconvenient to not get your chemo on time, and there is no evidence that waiting until an artificially determined number of white cells has anything to do with risk of infection. This is a very unscientific area."

• Neupogen

  I get a lot of questions about Neupogen, so I asked Dr Nichols, "What is Neupogen, and when would you use it?" He responded, "Neupogen (trade name for filgrastim or G-CSF) is a product that is used to prevent severe lowering of the white blood cell count associated with chemotherapy. It usually given by subcutaneous injection daily beginning the day after chemotherapy ends and for 7-10 days thereafter. The general recommendations for use in patients is as follows: I don't use this routinely in patients with good risk disease receiving 3 cycles of treatment. I would give it in this setting if the patient developed a fever associated with a low white count during the prior cycle of chemotherapy. We also consider it in patients with poor risk disease who are getting 4 cycles of chemotherapy and in all patients receiving salvage chemotherapy and all patients undergoing stem cell transplant. It is a very well tolerated medicine with the exception of sometimes causing bone pain from expansion of the bone marrow white cells. A similar drug (GMCSF, Leukine) is also sometimes used rather than G-CSF"

• Tumor Markers

  The tumor marker levels are a very important and convenient way to gauge the progress of chemotherapy. However, sometimes they go up after the first cycle. That does not mean that the chemo is not working. Dr Nichols notes that, "Sometimes there is a surge of markers with initiation of therapy, sometimes the markers are rising rapidly before and you catch it on an up phase. The practical aspect is that very rarely would I let the markers values at cycle two make me change or abandon therapy for first line treatment."

• Outpatient Fluids

  Back in the old days the treatment for testicular cancer was always done as an inpatient in the hospital. They did this so that they could constantly force fluid into the patient to ensure that there was no kidney damage. Nowadays, they've decided that this is overkill, and most people are healthy enough to take their chemo as an outpatient. Nevertheless, it is still important to drink as much as you can and to get the proper amount of fluid during the chemo infusion. Dr Nichols says that, "Most people would require a liter of normal saline before cisplatin, more with the etoposide (usually 500 cc) and a liter afterwards. So the patient should receive somewhere between 2.5 and 3 liters of fluid. Even at 500cc an hour, which is fast, this will take most of the day."

• Holidays

  Cancer can happen to you at any time of the year. Strangely, though, a lot of doctors and hospitals will try to get you to postpone your chemo because of holidays. That is not acceptable. If you begin chemotherapy in mid November, you could get moved around all over the place due to Thanksgiving, Christmas and New Years. Don't let them get away with this. As Dr Nichols says, "We make arrangements to treat our patients through the holidays on schedule. Cancer doesn't observe Thanksgiving..."

• Bleomycin Toxicity

  We mentioned before that Bleomycin can cause lung damage. Given the doses used in the standard chemotherapy protocols, the odds of this happening are very low. Nevertheless, make sure that the doctors are listening to your lungs periodically to check for this, and if you are experiencing symptoms such as a cough or shortness of breath, bring this to the attention of your doctor immediately.

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