Cisplatin treatment

THC is effective in several chemotherapy regimens, including methotrexate and the doxorubicin/cyclophosphamide/fluorouracil combination. Cisplatin treatment, however, is more resistant. Side effects of THC are generally well tolerated, and use may be limited in the elderly or with higher doses. Nabilone is a synthetic cannabinoid that is more effective than prochlorperazine in chemotherapy-induced emesis, including cisplatin. Its side effects are similar to THC. Levonantradol is another synthetic cannabinoid with antiemetic effects, and may be administered orally or intramuscularly. The side effect of dysphoria may limit its use. 

Importantly, the ERCCl/XPF structure-specific nuclease has an additional role in the repair of cisplatin adducts besides its function in NER the recombinational repair of interstrand crosslinks (19). ERCCl- or XPF-deficient hamster mutant cell lines are hypersensitive to DNA crosslink agents, much more so than to ultraviolet-induced pyrimide dimers, the classical substrates for NER (20,21). Moreover, co-localization of ERCCl foci and RAD51 foci in response to cisplatin treatment has recently been found and may represent recruitment of ERCCl/XPF to sites of recombination repair (22). Previous studies have shown that BRCAl, involved in homologous recombination repair, also plays a major role in the repair of cisplatin DNA damage (23). 

The other toxicities of carboplatin are generally milder and better tolerated than those of cisplatin. Nausea and vomiting, though frequent, is less severe, shorter in duration, and more easily controlled with standard antiemetics (for example compazine, dexamethasone, lorazepam) than that following cisplatin treatment. Renal impairment is infrequent, though alopecia is common, especially with the paclitaxel-containing combinations. Neu-... 

Reactions between cisplatin and serum albumin are thought to be the main route for platinum binding in human blood plasma. Several clinical and experimental observations have suggested that albumin-bound platinum may be anticancer active [47] [48]. Additionally, albumin binding may reduce some of the side-effects of cisplatin treatment, especially its nephrotoxicity [49]. The reaction of cisplatin with intact and chemically modified recombinant human albumin (rHA), and with HSA (human serum al-... 

Therapeutic applications Cisplatin has found wide application in the treatment of solid tumors such as metastatic testicular carcinoma in combination with vinblastine (see p. 390) and bleomycin (see p. 386), ovarian carcinoma in combination with cyclophosphamide (see p. 388), or alone for bladder carcinoma. Carboplatin is employed when patients cannot be vigorously hydrated as is required for cisplatin treatment, or if they suffer from kidney dysfunction or are prone to neuro- or ototoxicity. 

Gieterna JA, Meinardi MT, Messerschmidt J, et al. Circulating plasma platinum more than 10 years after cisplatin treatment for testicular cancer. Lancet, 2000, 355, 1075-1076. 

The major clinical problem encountered is the resistance against cisplatin. Some types of cancer are intrinsically insensitive to cisplatin treatment, whereas other cancers develop resistance during chemotherapy. This phenomenon limits the applicability of cisplatin to a relatively narrow range of tumors. The cisplatin-resistance mechanism seems to be multifactorial. Several main factors have been identified as potential modulators of cellular resistance, and are discussed below. 

Pratt CB, Goren MP, Meyer WH, Singh B, Dodge RK. Ifosfamide neurotoxicity is related to previous cisplatin treatment for pediatric sohd tumors. J Clin Oncol 1990 8(8) 1399 01. 

Pittelh MR. Neurotoxicity of two different cisplatin treatments. Rev Neurobiol 1990 26 459-64. 

Fia. 23. Serum Mn-SOD levels during the course of treatment of one patient with stage lib serous cystadenocarcinoma (CAP, cyclophosphamide, adriamycin, and cisplatin treatments SLO, second-look operation). 

The DACH complexes have been the focus of special attention [73] since several were found fully inhibitory to a line of L-1210 leukaemia made totally resistant to cisplatin treatment in vivo. This property is not universal, however, since the 2-hydroxymalonato compound, (10), was found to have greatly... 

Schilsky et al. [19] first recommended the use of hypertonic saline infusion after noting that when 3% saline was the vehicle for cisplatin, there was no change in either serum creatinine and creatinine clearance despite high dose cisplatin treatments. However, when 5 Cr-EDTA was used as a measure of glomerular filtration rate, a significant decrease in GFR was observed despite the use of 3% saline [12,13]. Recommendations regarding the use of hypertonic saline infusion to prevent high dose cisplatin nephrotoxicity must await a randomized study. 

More recently, attempts have been made to extend cisplatin treatment to other broad classes of tumors by raising the dose above the 5 mg/kg body... 

Pulmonary toxicity with bleomycin is an established reaction with a potentially serious, sometimes fatal, outcome. Concurrent use should be very closely monitored and renal function checked. One of the problems is that levels of creatinine may not accurately indicate the extent of renal damage both during and after cisplatin treatment. The renal toxicity of cisplatin may also develop rapidly. Other toxic effects on the vascular system can also occur. 

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