An adjusted dosing algorithm for the dosing of the anticancer drug carboplatin has been developed, that accounts for high BMI, low serum creatinine values and maximal calculated renal function. The hypothesis is that this new dosing algorithm provides a more accurate and safe dose than dosing according to the old standard of care.

Carboplatin is an alkylating anticancer drug that is used for the treatment of various types of cancer, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), malignant mesothelioma, ovarian cancer, and breast cancer. It is mostly given in combination with other chemotherapeutic drugs, but it can also be given as single agent.

Since carboplatin is highly eliminated by the kidneys, the dose needs to be adjusted for renal dysfunction. Furthermore, as there is clear correlation between the area under the concentration-time curve (AUC) of carboplatin and haematological toxicity and response rate, carboplatin is dosed per target AUC. For this, the standard pharmacokinetic formula [dose = clearance carboplatin x target AUC] is used.

the clearance is typically calculated using the cockcroft and gault (C-G) formula. In patients with high weight, or very low serum creatinine values the C-G-formula may overestimate the renal function, resulting in a potential overdose of carboplatin. the new developed dosing algorithm to be studied adjusts for high BMI and low serum creatinine values, in order to provide a more safe dose of carboplatin

Inclusion Criteria:

• histologically or cytologically proven advanced NSCLC, SCLC or ovarian cancer

• to be treated with carboplatin with a target AUC of 4, 5 or 6

• age 18 years or older

• WHO performance status 0 - 2

• adequate bone marrow and liver function defined as

  • haemoglobin ≥ 6.0 mmol/L
  • white blood cell count ≥ 3.0 * 109/L
  • absolute neutrophil count (ANC) ≥ 1.5 * 109/L
  • platelets ≥ 100/L
  • bilirubin ≤ 1.5 times ULN
  • ALAT and ASAT ≤ 2.5 times ULN (in case of liver metastases ≤ 5.0 times ULN).

• estimated life expectancy of at least 12 weeks

Exclusion Criteria:

• Treatment with carboplatin with a target AUC of <4
• active clinically serious infection
• history of a kidney allograft
• pregnant
• patients not suitable for follow-up
• pregnancy or breast-feeding