<b>Choosing A Chemotherapy Agent</b>

Of the <b>traditional</b> chemotherapy agents, doxorubicin, ifosfamide, and dacarbazine are the most effective against LMS. They are toxic. Ifosfamide MUST be given with mesna to protect the urinary system, and doxorubicin has a lifetime limit, because it destroys heart muscle. They both affect the bone marrow badly. Their response rate, if used as single agents, is in the late teens**, with very few if any complete responses. Their median response duration is often in months. If it is possible, testing of the tumor for resistance to these agents might be worthwhile before using them, because of the drug toxicity.
 
**[The clinical trials that established the rates of response for doxorubicin and ifosfamide included patients with GIST, previously included as a type of Gastrointestinal LMS.   GIST tumors are often completely resistant to chemotherapy agents, and carried a high death rate.  With the advent of Gleevec, GIST patients are no longer routinely categorized as LMS tumors.   With the elimination of GIST patients from LMS clinical trials, reported response rates and survival rates will rise.]
  
The idea behind the AIM regimen [adriamycin, ifosfamide, mesna] is to increase the response rate by using both agents, and the rate does go up to around 30%.  However duration of response and quality of response is still poor.  The MAID protocol adds dacarbazine to the previous cocktail.  There is no increase in survival time, but there is an increase in toxic side effects. Combinations are justified in situations where a quick response is imperative: to deal with life-threatening situations or with severe pain.  If your local oncologist is recommending a combination of chemotherapy agents for you, obtain a second opinion from a sarcoma oncologist.

<b>"The choice of combination chemotherapy versus sequential single agents is also quite controversial. Randomised prospective clinical trials on combination chemotherapy regimens such as MAID (mesna, adriamycin, ifosfamide, dacarbazine) and AIM (adriamycin, ifosfamide, mesna), have shown these to yield statistically improved rates of objective antitumour response. However, these do not translate into improvements in survival, and come at the cost of added toxicity and a decrease in quality of life. There is therefore good reason to choose sequential administration of active chemotherapy agents, to maximise the time of tumour control, and to minimise treatment-associated side-effects.</b> The exception to this is the preference of most physicians for combination chemotherapy in patients with acute pain or an immediate life-threatening problem (e.g. impending bronchial obstruction); in such cases, the greater likelihood of objective response would be worth the increased toxicity of combination therapy in an otherwise healthy patient for whom such aggressive therapy would be reasonable." [1]

"Local instillation of chemotherapy, such as infusion into the peritoneal cavity as treatment for intraperitoneal STS, remains popular in certain centres. However, such local infusional therapy has never been shown to be superior to systemic administration of chemotherapy in any clinical trial. "[1] However, there may be a place for Intraperitoneal Hyperthermic Chemotherapy.   See the web page on Hyperthermia on this site.

" There appears to be a relation between the delivered dose of certain drugs, (e.g. doxorubicin and ifosfamide), and objective antitumour response rates. It is unclear whether these responses last long enough to justify the increased toxicities (myelosuppression, mucositis, nephrotoxicity, etc) that accompany therapy at higher doses. Physicians must therefore carefully weigh the available evidence and the therapeutic goals for an individual patient to decide how best to use chemotherapy. <b>There is no global consensus on the best way to apply 'standard' chemotherapy for the management of sarcomas."</b>[1]

<b>"Certain [sarcoma] subtypes have virtually no chance of major clinical response to conventional cytotoxic therapies, so whenever possible, these patients should be offered treatment with promising new agents in clinical trials. Included in this category of sarcomas with primary chemotherapy resistance would be most non-uterine leiomyosarcomas."</b>[1]

NOTE 1: Newer agents such as Temozolomide, Gemcitabine, Navelbine and ET-743 are useful, but also do not cure LMS.  Doxil, a much less toxic form of doxorubicin than Adriamycin, is not widely tested yet.
NOTE 2: All chemotherapy agents are cell poisons.  Side effects vary from agent to agent and person to person, but there are good medicines to control diarrhea, vomiting, and other side effects.  These medicines make a big difference.

[1] Singer, S, Demetri, GD, Baldini, EH, Fletcher, CDM.  "Management of Soft-tissue sarcomas: An Overview and Update". Lancet Oncology. Oct 2000