Cases chemotherapy

Cumulative organ toxicity also presents a significant obstacle for effective chemotherapy. In many cases, the severity of the toxicity impedes the broader use of an agent. Other specific toxicities are associated with specific agents, for example cardiotoxicity with adriamycin (32), renal toxicity with i7j -platinum (28), and neurotoxicity with vincristine (49). 

Most recently, a phase-I-study defined a dose of 13-ris-retinoic acid that was tolerable in patients after myeloablative therapy, and a phase-III-trial showed that postconsolidation therapy with 13-cis-retinoic acid improved EFS for patients with high-risk neuroblastoma [7]. Preclinical studies in neuroblastoma indicate that ATRA or 13-cw-RA can antagonize cytotoxic chemotherapy and radiation, such that use of 13-cis-RA in neuroblastoma is limited to maintenance after completion of cytotoxic chemotherapy and radiation. It is likely that recurrent disease seen during or after 13-cis-RA therapy in neuroblastoma is due to tumor cell resistance to retinoid-mediated differentiation induction. Studies in neuroblastoma cell lines resistant to 13-cw-RA and ATRA have shown that they can be sensitive, and in some cases collaterally hypersensitive, to the cytotoxic retinoid fenretinide. Here, fenretinide induces tumor cell cytotoxicity rather than differentiation, acts independently from RA receptors, and in initial phase-I-trials has been well tolerated. Clinical trials of fenretinide, alone and in combination with ceramide modulators, are in development. 

TNF was originally identified because of its cytotoxic activity against some tumor cell lines and its ability to induce hemorrhagic necrosis of solid tumors in various animal models. However, the clinical use of TNF as an anticancer drug has been so far limited by its severe cardiovascular side effects. Therefore, TNF treatment is limited to regional and local administration of high doses of TNF, often in combination with chemotherapy, as accomplished in isolated limb and isolated hepatic perfusion (ILP and IHP, respectively) [5]. In the case of ILP, typically metastases are treated, patients benefit from this procedure by salvage of limbs from a loss by amputation. 

Uric acid excretion is reduced in patients with chronic kidney disease, putting them at risk for hyperuricemia. In patients with persistently acidic urine and hyperuricemia, uric acid nephrolithiasis can occur in up to 25% of patients in severe cases, uric acid stones can cause nephropathy and renal failure. Extreme hyperuricemia can occur because of rapid tumor cell destruction in patients undergoing chemotherapy for certain types of cancer (see Chap. 85). 

About 10% of infected patients develop reactivation TB, with half occurring in the first 2 years after infection.2 6 12 Upper lobe pulmonary disease is the most common (85% of cases).2 Caseating granulomas result from the vigorous immune response, and liquefaction leads to local spread. Eventually, a pulmonary cavity results, and this provides a portal to the outside that allows for person-to-person spread. Bacterial counts in the cavities can be as high 1011 per liter of cavitary fluid (108 per milliliter).2,15 Prior to the chemotherapy era, pulmonary TB usually was associated with hypoxia, respiratory acidosis, and eventually death. 

Diarrhea may occur from effects of chemotherapy on the lower portion of the GI tract. Diarrhea can be severe and may need to be treated with intravenous fluids and electrolytes. Infectious causes, such as C. difficile, should be ruled out. Pharmacologic therapy of diarrhea can range from loperamide or cholestyramine to octreotide for severe cases of diarrhea that are refractory to usual treatments. 

Both endocrine therapy and chemotherapy are used in patients with an uncertain endocrine response category unless the patients are low risk, in which case they may just try endocrine therapy alone. 

Cytotoxic chemotherapy is eventually required in most patients with metastatic breast cancer. Patients with hormone-receptor-negative tumors require chemotherapy as initial therapy of symptomatic metastases. Patients who respond initially to hormonal manipulations eventually cease to respond and go on to require chemotherapy. The median duration of response is 5 to 12 months, but some patients will have an excellent response to an initial course of chemotherapy and may live 5 to 10 years or longer without evidence of disease. In general, median survival of patients after treatment with commonly used drug combinations for metastatic breast cancer is 14 to 33 months. The median time to response has ranged from 2 to 3 months in most studies, but this period depends in large part on the site of measurable disease. The median time to appearance of response is between 3 and 6 weeks in patients whose disease is primarily in the skin and lymph nodes, 6 to 9 weeks in patients with metastatic lung involvement, 15 weeks in patients with hepatic involvement, and nearly 18 weeks in patients with bone involvement. Thus it is often the case that an immediate response to therapy is not... 

Doublet chemotherapy regimens are superior in response to single-agent regimens and should be used when the patient can tolerate the associated toxicity. Platinum-containing doublets are first-line treatment in most cases. 

Small cell lung cancer typically presents as extensive disease (approximately 60% to 70% of new cases) and progresses very quickly. Small cell carcinomas are very responsive to chemotherapy and radiation. Radiotherapy became the standard in 1969, when a randomized trial showed that it offered the potential for cure, whereas surgery did not.20 For the vast majority of patients, chemotherapy with or without radiotherapy is the treatment of choice. Even after a complete response to therapy, the cancer usually recurs within 6 to 8 months, and survival time following recurrence is typically short ( 4 months). This yields a typical survival rate of 14 to 20 months for limited disease and 8 to 13 months for extensive disease.33 Table 87-6 illustrates the general treatment path of SCLC. 

Chemotherapy extravasation may be avoided in many cases by the use of successful prevention strategies. The most important preventative measure is proper patient education. 

Therapeutic modalities to treat extravasation events consist of specific antidotes to halt or decrease the severity of local tissue necrosis. It should be noted that only one-third of extravasation events will lead to local tissue necrosis, and most studies of antidotes are in animal models or isolated case reports. Antidotes either disperse or bind the chemotherapy agent and accelerate the removal of the agent from the tissues. Specific antidotes and their uses are presented in Table 96-16. 

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