What Chemotherapy to Try Next

You should begin chemotherapy if your cancer:

• is growing in spite of various hormonal therapies or immune therapy
• is hormone-receptor-negative
• is in the liver or throughout your lung tissue (called lymphangitic spread)

This may be your first treatment for metastatic disease, or you may be coming back for a fourth try or more. There are many different combinations with good response rates. So you still have a chance to respond to a new treatment. You may not have had an impressive response to one chemotherapy plan, but that doesn't mean you won't have an encouraging response to another.

Remember, quality of life is important. You may decide against "the strongest" therapy if it has the most troubling side effects. You can try something less toxic to start off and still have a good response. Later on, if you need something more powerful—and you have the strength—you may choose to try a stronger drug.

If you have never had chemotherapy before, your medical oncologist might choose a tried-and-true combination of drugs, with response rates ranging from 35% to 60%:

• AT – Adriamycin (chemical name: doxorubicin) and Taxotere (chemical name: docetaxel)
• AC ± T – Adriamycin with cyclophosphamide, with or without Taxol (chemical name: paclitaxel) or Taxotere (chemical name: docetaxel)
• CMF – cyclophosphamide, methotrexate, and fluorouracil ("5–FU" or 5–fluorouracil)
• CEF – cyclophosphamide, Epirubicin (similar to Adriamycin), and fluorouracil ("5–FU" or 5–fluorouracil)
• FAC – fluorouracil ("5–FU" or 5–fluorouracil), Adriamycin, and cyclophosphamide
• CAF – cyclophosphamide, Adriamycin, and fluorouracil ("5 FU" or 5 fluorouracil)

FAC and CAF differ by dose and frequency.

As this list shows, Taxol or Taxotere (chemical name: docetaxel) can be given along with other medications: Adriamycin with cyclophosphamide, then Taxol, or Adriamycin with Taxotere.

A study that compared Taxol to Taxotere along with other chemotherapy showed that the regimen containing Taxotere was more effective for metastatic disease than Taxol after anthracycline chemotherapy (Adriamycin) has stopped working. It was better in terms of shrinking the cancer, in how long the response lasted, in the time it took for the disease to progress, and in overall survival.

In addition, data show that Abraxane, a newer taxane, may also work better than Taxol or Taxotere with fewer side effects.

Single-agent therapy

A single chemotherapy agent is often recommended before a combination is given. This is because you can get significant benefits with fewer side effects.

You may be prescribed single-agent therapy with a taxane (Taxotere, Taxol, or Abraxane), a chemotherapeutic agent such as Adriamycin, or an immune therapy such as Herceptin.

• Taxanes (Taxotere, Taxol, or the newest medication, Abraxane) give a better response rate than Adriamycin (more patients whose cancer shrinks or disappears), with less nausea, vomiting, and mouth sores. Their impressive response rates average around 30%, and range between 15% and 60%.
  Taxotere or Taxol, given weekly in relatively low doses, is very effective and is associated with fewer side effects (such as low blood counts, hair loss, and nerve problems) than when given every three weeks. Abraxane is also given once a week and does not require pre-treatment with steroids.
• Although Herceptin (chemical name: trastuzumab) is an immune therapy, not chemotherapy, it is also sometimes prescribed for HER2-positive metastatic disease as single-agent therapy. It is given weekly or every three weeks and has few side effects.

Combination therapy

Your doctor may recommend a combination chemotherapy regimen that uses a taxane or Adriamycin. These include: CAF, FAC, CEF, or AC then Taxol, or AT (Adriamycin and Taxotere). Steroids are given before Taxol or Taxotere to further lessen side effects.

Abraxane can be used with Herceptin and also as a triple combination with Herceptin and Gemzar (chemical name: gemcitabine).

Discuss the pros and cons of each approach with your doctor, including important lifestyle considerations.

Drugs to try after combination therapy

If you have already tried a regimen containing Adriamycin, and one containing a taxane, most doctors would next recommend, in this order:

• CMF - cyclophosphamide, methotrexate, and fluorouracil ("5-FU" or 5-fluorouracil)
• Single-agent Navelbine (chemical name: vinorelbine) or Gemzar. Each can be used to help keep the tumor and its symptoms under control without causing too many side effects (including less hair loss). The response rate is 20% to 40%, and lasts about eight months. Both drugs work well even if you have other illnesses, such as diabetes.
• Xeloda (chemical name: capecitabine) has been shown to be effective in some women whose cancer has progressed in spite of receiving Taxol, Taxotere, and Adriamycin. Xeloda is in an inactive form when you take it (by pill). Your liver, then the tumor, converts it to its active cancer-fighting form, 5-fluorouracil. (Cancer cells contain high levels of an enzyme that converts Xeloda to its active state.) This two-step activation process means that a higher concentration of the drug lands in the cancer tissue, not the normal tissue. Side effects are mild to moderate (mostly diarrhea and vomiting), with very little effect on the immune system, and no hair loss.

If none of these regimens works, additional programs can include:

• Ixempra (chemical name: ixabepilone) was approved by the FDA in October 2007 to treat cancers that are resistant to treatment with anthracyclines, taxanes (Taxotere, Taxol, and Abraxane), and Xeloda. Ixempra may also be given in combination with Xeloda.
• Mitomycin (chemical name: mutamycin) and Vincristine (brand names: Oncovin, Vincasar PES, Vincrex) or another drug from the same class of vinca alkaloid drugs
• 5-fluorouracil (5-FU) by continuous infusion or in combination with leucovorin (response rates range from 10% to 40%)
• mitoxantrone (Novantrone), 5-FU, and leucovorin
• high dose methotrexate and leucovorin
• a new unknown-at-this-moment experimental regimen

Most of the regimens presented here can be used to control the cancer and preserve the most reasonable quality of life. Careful use of steroids can reduce side effects and improve your appetite and how you feel. Megace can be added to any regimen to improve your interest in food.