Sarcoma, chemotherapy

Theis JG, Chan HS, Greenberg ML, et al. Increased systemic toxicity of sarcoma chemotherapy due to combination with the P-glycoprotein inhibitor cyclosporin. Int J Clin Pharmacol Ther 1998 36(2) 61-64. 

Kaposi sarcoma (KS) - an angiogenic-inflammatory neoplasm - is the most prevalent cancer in HIV-infected patients and its appearance is preceded by infection with human Heipesvitus-8 (HHV-8). Although chemotherapy has become the treatment of choice approved by the FDA, there are also good response rates in patients treated with IFN-a. Fortunately, today highly active antiretroviral therapy (HAART) has dramatically decreased the incidence of KS in AIDS patients. 

Intron A interferon a-2b Schering-Plough Hairy cell leukemia, genital warts, AIDS-related Kaposi s sarcoma, hepatitis C, hepatitis B, malignant melanoma, follicular lymphoma in conjunction with chemotherapy... 

Hairy cell leukemia Genital warts AIDS-related Kaposi s sarcoma Non-A non-B hepatitis Hepatitis B Malignant melanoma Chronic viral hepatitis C Follicular lymphoma with chemotherapy June 1986 June 1988 Nov. 1988 Feb. 1991 July 1992 Dec. 1995 March 1997 Nov. 1997... 

Abe S, Tokizaki T, Miki Y, Tateishi A, Ogawa K, Nakano H, Matsushita T (2005) Hyperthermic isolated regional perfusion with CDDP for bone and soft-tissue sarcoma of the lower limb pharmacokinetics, thermal dose, toxicity, and feasibility. Cancer Chemotherapy and Pharmacology 56 55-62. 

This is an unusual drug in that it contains a metal atom, platinum (Pt) in this case. Cisplatin reacts with DNA to cross-link bases, disrupting normal DNA structure and function. This agent has found broad use in cancer chemotherapy, including efficacy in tumors of the testis, ovary, bladder, head and neck, thyroid, cervix, and endometrium. It is also active against neuroblastoma and osteogenic sarcoma. 

Concurrent therapy for the treatment of more than three brain metastases using paclitaxel and radiation has been explored in a phase III trial (144). The hypothesis here being that high-dose paclitaxel in combination with cranial radiation should improve local control while providing systemically active amounts of chemotherapy. Unfortunately, there was no statically significant improvement in survival seen. There is certainly a place to further explore the benefits and toxicides experienced with concurrent taxane-based therapy with radiation in metastatic disease. The role of the taxanes in concurrent chemoradiotherapy with sarcomas and pediatric tumors has not been explored at this time. 

Sarcomas are tumors of mesenchymal origin, arising in skeletal tissues and extra-skeletal connective tissues including the nerves. They are very rare and mainly effect a younger population. Sarcomas of soft tissues are relatively insensitive to drug treatment and are therefore not discussed in detail in this chapter. A systematic review of fourteen trials of doxorubicin-based adjuvant chemotherapy for the treatment of soft tissue sarcomas involving 1568 patients concluded Doxorubicin-based adjuvant chemotherapy appears to significantly improve time to local and distant recurrence and overall recurrence-free survival in adults with localised resectable soft tissue sarcoma. There is some evidence of a trend towards improved overall survival (see Sarcoma Meta-analysis Collaboration, 1999). 

Skeletal sarcomas can be largely divided into osteosarcomas on one hand and the Ewings family of sarcomas, including peripheral neuro-ectodermal tumors or PNETs, on the other hand. Both groups share a sensitivity to chemotherapy and need to be managed by multidisciplinary teams to optimize potential curability. 

Sarcoma Meta-analysis Collaboration. Adjuvant chemotherapy for localised resectable soft tissue sarcoma in adults. Cochrane Database Syst Rev 1999. Issue 4. 

The treatment of Hodgkin s disease also illustrates the use of combined modalities, that is, radiation plus chemotherapy. The combined modality approach to several childhood tumors (e.g., Ewing s sarcoma, Wilms tumor, and rhabdomyosarcoma) has dramatically increased the cure rates for these diseases. 

Using the more versatile tool of aromatic cyclodehydration (Scheme 98), Sawa and Ikekawa have prepared a variety of dibenzo[a,g]quinolizinium derivatives for use in cancer chemotherapy. Their results are described in a large number of Kokai (e.g. 75JAP(K)75154295). From these, it is clear that the compounds of greatest interest bear a hydroxy group or hydroxy derivative at position 8. In a German patent (75GEP2520524) it was claimed that 8-hydroxy-9-methoxydibenzo[a,g]quinolizinium bromide (231) increased the survival time of mice infected with sarcoma 180 and leukemia 1210 by 100% and 240% respectively. 

E. Therapeutic response According to the product label, studies have shown that Rofewn-A can normalize serum transaminases, improve Uver histology, and reduce viral load in patients with chronic hepatitis C virus (HCV) infection. Other studies have shown that Roferon-A can produce clinically meaningful tumor regression or disease stabilization in patients with hairy-cell leukemia or in patients with AIDS-related Kaposi s sarcoma. In Ph-positive CML, Roferon-A supplemented with intermittent chemotherapy has been shown to prolong overall survival and to delay disease progression compared to patients treated with chemotherapy alone. In addition Roferon-A has been shown to produce sustained complete cytogenetic responses in a small subset of patients with CML in chronic phase. 

Taxol is a natural product that has impacted the lives of hundreds of thousands of people. Since 1992, it has been the API in certain chemotherapy agents provided to patients suffering from a variety of cancers and is approved for the treatment of ovarian, breast, non-smaU-ceU lung cancers and AIDS-related Kaposi s sarcoma in over 50 countries. 

Galanis E, Okuno SH, Nascimento AG, Lewis BD, et al. 2005. Phase I—II trial of ONYX-015 in combination with MAP chemotherapy in patients with advanced sarcomas. Gene Ther. 12 437—445. 

Ewing s sarcoma is the second most common malignant bone tumor in children. The majority of patients have microscopic metastases at diagnosis the lung is the most common metastatic site. This sarcoma is a relatively rare disease with limited therapeutic options. The majority of patients are initially responsive to chemotherapy with vincristine, doxorubicin (Adriamycin), and cyclophosphamide. However, relapsed disease is usually extremely difficult to treat because of its resistance to chemotherapy (Zhou et al., 2001). 

Northfelt, D. W., Dezube, B. J., Thommes, J. A., et al. Efficacy of PEGylated-liposo-mal doxorubicin in the treatment of AIDS-related Kaposi s sarcoma after failure of standard chemotherapy. J. Clin. Oncol. 15(2) 653-659. 1997. 

Primary chemotherapy (prior to local surgery) is now extensively used in patients with osteogenic sarcoma and has facilitated limb-sparing procedures. Primary chemotherapy is also being evaluated in breast cancer to "downstage" patients prior to surgery. 

Meistrich ML, Wilson G, Brown BW, da Cunha MF, Lipshultz LI (1992) Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas. Cancer, 70 2703-2712. 

Tucker MA, D Angio GJ, Boice JD, Strong LC, Li FP, Stovall M, Stone BJ, Green DM, Lombardi F, Newton W (1987) Bone sarcomas linked to radiotherapy and chemotherapy in children. N Engl J Med, 317 588-593. 

Kaposi s sarcoma/ hepatitis C/follicular lymphoma in conjunction with chemotherapy/ hepatitis B... 

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