
<b>The role of chemotherapy in metastatic or unresectable sarcomas </b>

"The role of chemotherapy in advanced STS is controversial and, at present, the treatment of metastatic STS represents palliative, not curative, therapy. ,,, Clearly, there is a pressing unmet medical need for improved therapies ,,,  However, currently available drugs can often yield important benefits when used judiciously, and can prolong life and decrease symptoms. ,,, Certain 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, for example, ,,, most non-uterine leiomyosarcomas ,,, Given the range of possibilities, the choice of chemotherapy must be left to the individual physician, based on specific features of the sarcoma (type, location, symptoms, or immediate threat to life, etc), the overall health status of the patient (co-morbid diseases, etc) and the patient's preferences." [1]

"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, dacarbazine), 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. The exception to this is the preference of most physicians for combination chemotherapy in patients with acute pain or an immediate life-threatening problem (eg 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]

",,,The discussion of the relevance of dose and dose-intensity in STS management has generated far more heat than light. There appears to be a relation between the delivered dose of certain drugs, (eg       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. There is no global consensus on the best way to apply 'standard' chemotherapy for the management of sarcomas." [1]

1. Samuel Singer, George D Demetri, Elizabeth H Baldini, and Christopher DM Fletcher
Management of soft-tissue sarcomas: an overview and update
Lancet Oncology, Volume 1, Number 2,  01 October 2000

We know that Demetri favors single agent chemotherapy agents, not in high dose, for judicious use in extending survival time with a good quality of life in inoperable stage IV LMS.   There is a place for cocktails in stage IV, however.  

Cocktails are sometimes used where an LMS tumor is inoperable, but with some judicious use of chemo and/or radiation, it MIGHT be made operable.  This is called neoadjuvant treatment.   In the case of stage III LMS, there would still be the possibility of a cure.  In stage IV LMS, there might be a chance of a prolonged remission.

And sometimes there is very vicious, aggressive stage IV disease, where cocktails are used to prevent or to gain control of an onslaught of metastases.  

And sometimes there are positive compromised margins on surgical resection, and radiation cannot be used in that particular site.  In these latter cases, sometimes chemotherapy combinations [chemo cocktails] are used.  

I am listing a few of the chemotherapy cocktail choices used for LMS below, along with a Pubmed/Medline search string for their clinical trials.

<b>WARNINGS:
 Be careful when you are reading, some clinical trials are for sarcomas, not just LMS, and may not be as relevant as clinical trials dealing with LMS, as some sarcomas are relatively radiosensitive or chemosensitive.   Sometimes the clinical trials dealing with LMS include GIST, which is incredibly chemo resistant, so the response rates for LMS are erroneously lowered. Sometimes there are no clinical trials dealing with LMS alone. </b>

&&url is also a good site to search for results of clinical trials, especially of the newer agents. You will have to go to the site and search the abstracts with keywords of the chemotherapy agent AND sarcoma.
