Cisplatin dosage

A German study randomized 98 patients with unresectable hypopharyngeal head and neck carcinoma to sequential or concomitant chemoradiotherapy (64). Patients on the sequential arm received two courses of cisplatin (25 mg/m2 for 5 d) and continuous infusion 5-FU (750 mg/m2 for 5 d) followed by G-CSF for 6 d. The second cycle was repeated on d 14 and then followed by standard radiotherapy. Identical dosages of chemoradiotherapy were used in the concomitant arm but incorporated a 21-d interval between each chemotherapy cycle and G-CSF support. Sequential treatment resulted in a CR of 49% in comparison to the concomitant arm of 57%. At 2-yr, the median survival was improved in the concomitant arm (53% vs 33%). However, one-third of the initial patients enrolled were withdrawn from study due to medical or socioeconomic problems whether this resulted in a significant disparity between the two different treatment arms was not noted. Mature data from this trial have not been published to date. 

The RT consisted of 45 Gy in 3 wk using 1.5 Gy bid concurrent with either cisplatin/etoposide or carboplatin/vindesine after the same drugs had been given alone at higher dosage. Acute toxicity was acceptable and treatment-related deaths were 9% or... 

Loehrer PJ, Elson P, Dreicer R, et al. Escalated dosages of methotrexate, vinblastine, doxorubicin, and cisplatin plus recombinant human granulocyte colony-stimulating factor in advanced urothelial carcinoma an Eastern Cooperative Oncology Group trial. J Clin Oncol 1994 12 483-488. 

Since the late seventies, the clinical application of cisplatin has increased enormously16-18), mainly as a result of improved administration procedures and its use in combination therapy, i.e. the simultaneous application of a variety of synergistic antitumor drugs. Nowadays, usually a dosage per patient of about 100 mg of cisplatin per m2 body surface area, dissolved in saline, is given intravenously every month by standard administration protocols. 

A variety of other compounds have mechanisms of action that involve alkylation. These include procarbazine, dacarbazine, altretamine (hexamethylmelamine), cisplatin, and carboplatin. Dosages and major toxicities are listed in Table 55-2. 

IFOSFAMIDE CISPLATIN t risk of neurotoxicity, haematotoxicity and tubular nephrotoxicity of ifosfamide due to t plasma concentrations of ifosfamide Cisplatin tends to cause renal damage, which results in impaired clearance of ifosfamide Do renal function tests before initiating therapy and during concurrent therapy, and adjust dosage based on creatinine clearance values. Advise patients to drink plenty of water -vigorous hydration - and consider mesna therapy for renal protection... 

Asymptomatic sinus bradycardia (for example 30-40/ minute) is observed within 30 minutes to 2 hours after the start of cisplatin infusion. When cisplatin is withdrawn normal rhythm is restored. Becanse patients who receive platins are not rontinely monitored, drug-induced sinus bradycardia may not be detected in practice. However, several case reports have inclnded heavily pretreated patients, which makes a direct relation between cisplatin administration and the onset of cardiotoxic s)miptoms much more difficult to assess. In concinsion, no dosage adjustment appears to be warranted in patients with cisplatin-induced sinus bradycardia however, attention shonid be paid to patients with resting bradycardia or those using medications known to slow the heart rate (46,47). 

In several studies, intravenous amifostine (910 mg/m ) preserved glomerular filtration rate when it was co-administered with cisplatin-containing regimens (213). Even after two cycles containing intravenous cisplatin 50 mg/m plus intravenous ifosfamide and etoposide or paclitaxel, glomerular filtration rate can fall by more than 30%, but concomitant use of amifostine prevented this. Even lower dosages of intravenous amifostine (for example 740 mg/m ) may be effective (220,221). 

Meerum Terwogt JM, Groenewegen G, Pluim D, Maliepaard M, Tibben MM, Huisman A, ten Bokkel Huinink WW, Schot M, Welbank H, Voest EE, Beijnen JH, Schellens JM. Phase I and pharmacokinetic study of SPI-77, a hposomal encapsulated dosage form of cisplatin. Cancer Chemother Pharmacol 2002 49(3) 201-10. 

Thomas H, Derbyshire N, Jones HB, Moores M (2012) Evaluation of novel renal biomarkers with a cisplatin model of kidney injury gender and dosage differences. 

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