Chemotherapy case studies

Ojima, I. (2008) Guided molecular missiles for tumor-targeting chemotherapy case studies using the 2nd-generation taxoids as warheads. Accounts of Chemical Research 41, 108-119. 

Webb, G.F. Resonance phenomena in cell population chemotherapy models. Rocky Mountain J. Math. 1990, 20 1195-1216. Andersen, L.K., Mackey, M.C. Resonance in periodic chemotherapy a case study of acute myelogenous leukemia. J. Theor. Biol. 2001, 209 113-130. 

Case study level Mb - Oral chemotherapy - see page 181... 

Data regarding the toxic effects of hydrazines in humans are limited to a few case studies of accidental exposure and chemotherapy trials in cancer patients. Studies consistently indicate that the central nervous system is the primary target for hydrazine and 1,1 -dimethylhydrazine following inhalation, oral, and dermal exposures. In some cases, neurological effects were delayed, but most effects were observed either during exposure or soon after. Quantitative data on human exposures are available only for oral exposures of intermediate durations. 

In Chapter 20, titled Alexander s Tumor, a tragic case study is presented about a brain tumor in a young child that was linked to SV40, it being found in the tumor. The traditional chemotherapy treatments were unbearable, and the child died in his mother s arms. 

Skin DOX chemotherapy has been associated with the development of subacute cutaneous lupus erythematosus (SCLE). This has been observed with the combination of cyclophosphamide and DOX. In a case study SCLE was observed in a patient with metastatic breast cancer treated with DOX alone After her second cycle of chemotherapy a pruritic facial rash developed and subsequently worsened with two further cycles of DOX. Treatment was initiated and DOX chemotherapy was discontinued and the SCLE resolved after 5 weeks. 

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. 

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... 

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. 

A study of 148000 subjects by Lanza and colleagues (1987) reported 36 individuals with myeloperoxidase deficiency, 10 of whom were completely deficient a further 2 individuals with total deficiency were identified from familial studies. Of the 12 patients with total deficiency, 7 had either benign or malignant tumours, but none was undergoing radio- or chemotherapy at the time of analysis hence, the myeloperoxidase deficiency could not be attributed, in these cases, to the therapy used for treatment of the malignant disease. These findings imply either that the tumour somehow affects the expression of myeloperoxidase in these patients, or that myeloperoxidase-deficient individuals perhaps have an increased incidence of tumours. Much follow-up work is needed for these studies on myeloperoxidase-deficient neutrophils in order to evaluate these proposals. 

Rouesse J, Friedman S, Sarrazin D, et al. Primary chemotherapy in the treatment of inflammatory breast carcinoma a study of 230 cases from the Institut Gustave-Roussy. J Clin Oncol 1986 4 1765-1771. 

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