Management of Recurrent Ovarian Cancer in Older Women

Abstract

Data on the treatment of recurrent ovarian cancer in the elderly has relied mostly on selected pilot studies. The largest study, ICON4 analyzes the elderly subset and does suggest that patients over 65 benefit from treatment with carboplatin + paclitaxel when the disease is categorized as platinum-sensitive as compared to single agents or other combinations. When the disease is platinum-resistant, preliminary results of the AURELIA study indicate that bevacizumab adds to the effect of chemotherapy, and this may also be applicable to the elderly. Nevertheless, there are a number of considerations relating to co-morbid conditions, adherence to treatment, and drug interactions that may pose a challenge in any one elderly individual undergoing chemotherapy treatments. Detection of early recurrences may be important, but this has not been studied specifically in an elderly population.

Appendix (From C. Aghajanian for Gynecologic Oncology Group, January 2012)

Reprinted with permission from GOG Statistical Center, Elm & Carlton Streets, Buffalo, NY 14263-0001.

Carboplatin Dose Calculation Instructions

The Cockcroft-Gault formula will be used in GOG trials.

Conversion of IDMS creatinine levels to “non-IDMS” values will not be permitted.

A carboplatin calculation tool is available on the GOG website (Web Menu, Tools).

Dosing of Carboplatin

The carboplatin dose will be calculated to reach a target area under the curve (AUC) according to the Calvert formula using an estimated glomerular filtration rate (GFR) from the Cockcroft-Gault formula.

The initial dose of carboplatin must be calculated using GFR. In the absence of renal toxicity greater than or equal to CTCAE grade 2 (serum creatinine >1.5 × ULN) or toxicity requiring dose modification, the dose of carboplatin will not need to be recalculated for subsequent cycles but will be subject to dose modification for toxicity as noted in the protocol.

At the time of dose modification, if the patients age has changed (the patient has had a birthday), the site can use the current age.

In patients with an abnormally low serum creatinine (less than 0.7 mg/dl), the creatinine clearance should be estimated using a minimum value of 0.7 mg/dl.

For trials where patients enter and are treated within less than or equal to 12 weeks of surgery: If a more appropriate (higher) baseline creatinine value is available from the preoperative period (within 4 weeks of surgery date), that value may also be used for the initial estimation of GFR.

Calvert formula:

$$\text{Carboplatin}\text{dose}\left(\text{mg}\right)=\text{Target}\text{AUC}\times(\text{GFR}+25)$$

Note: The GFR used in the Calvert formula should not exceed 125 ml/min.

$$Maximum\text{{0.17em}}\text{carboplatin}\text{{0.17em}}\text{dose}\text{{0.17em}}\left(\text{mg}\right)=\text{Target}\text{{0.17em}}\text{AUC}\text{{0.17em}}\left(\text{mg}\text{}/\text{}\text{ml}\times \mathrm{min}\right)\times 150\text{{0.17em}}\text{ml}\text{}/\text{}\mathrm{min}.$$

The maximum allowed doses of carboplatin are:

• AUC 6  =  900 mg

• AUC 5  =  750 mg

• AUC 4  =  600 mg

For the purposes of this protocol, the GFR is considered to be equivalent to the estimated creatinine clearance. The estimated creatinine clearance (ml/min) is calculated by the method of Cockcroft-Gault using the following formula:

$$ \text{Creatinine} \text{clearance}\left(\text{ml}\text{}/\text{}\mathrm{min}\right)=\frac{\left[140-\text{Age} \left(\text{years}\right)\right]\times \text{Weight} \left(\text{kg}\right)\times 0.85}{72\times \text{serum} \text{creatinine} \left(\text{mg}\text{}/\text{}\text{dl}\right)}$$

Notes:

Weight in kilograms (kg):

Body mass index (BMI) should be calculated for each patient. A BMI calculator is available at the following link: http://www.nhlbisupport.com/bmi/

Actual weight should be used for estimation of GFR for patients with BMI of less than 25.

Adjusted weight should be used for estimation of GFR for patients with BMI of greater than or equal to 25.

Adjusted weight calculation:

$$\text{Ideal}\text{{0.17em}}\text{weight}\left(\text{kg}\right)=\left(\left(\left(\text{Height} \left(\text{cm}\right)/2.54\right)-60\right)\text{{0.17em}}\times 2.3\right)\text{{0.17em}}+45.5 $$

$$ \text{Adjusted}\text{{0.17em}}\text{weight}\text{{0.17em}}\left(\text{kg}\right)=\left(\left(\text{Actual}\text{{0.17em}}\text{weight}-\text{{0.17em}}\text{Ideal}\text{{0.17em}}\text{weight}\right)\times 0.40\right)+\text{Ideal}\text{\{0.17em}\text{weight}$$

The Cockcroft-Gault formula above is specifically for women (it includes the 0.85 factor).

At the time of a dose modification for toxicity:

If the creatinine at the time of a dose modification is lower than the creatinine used to calculate the previous dose, use the previous (higher) creatinine; if the creatinine at the time of a dose modification is higher than the creatinine used to calculate the previous dose, use the current (higher) creatinine. This will ensure that the patient is actually receiving a dose reduction.

Moreover, the AURELIA study results presented at the May 2012 American Society of Clinical Oncology (ASCO) meeting reported delays in disease progression when bevacizumab was added to either paclitaxel, pegylated liposomal doxorubicin or topotecan versus either of the agents by themselves –thus encouraging use of combined treatments.