Cancer Treatment Today

Lay Summary: Gemcitabine and Carboplatin is an acceptable regimen for recurrent or progressive breast cancer.

Gemcitabine and carboplatin have significant preclinical synergy, and both provide synergistic antitumor activity in metastatic breast cancer (MBC) when used in combination with trastuzumab. The gemcitabine/ cisplatin combination is highly active in MBC with response rates (RRs) of approximately 50% in anthracycline- and taxane-pretreated patients and up to 80% in untreated subjects.

Gemcitabine is an active drug in breast cancer: 37% of responses as first line, 26% as a second line and 18% as third line; The responses with Gemcitabine plus cisplatin is patients with MBC is: 40% to 80%. Carboplatin has not been identified as a very active drug in breast cancer, however gemcitabine has a synergism with this drug. The rational for combining gemcitabine and carboplatin is based on their single-agent activities in metastatic breast cancer, the activity of this combination in other malignancies and on the fact that carboplatin has demonstrated efficacy comparable with cisplatin in several tumor types. Several phase II studies show respectable activity of this combination for breast cancer. While NCCN did not list this as a preferred combination, it lists both drugs as being active. The extent of evidence supporting this combination is on par with that for other frequently used second line combinations.

The most recent phase II trial has been completed and published: Combination Gemcitabine, Carboplatin With or Without Trastuzumab in Patients With Metastatic Breast Cancer, NCT00193076. In patients with HER2-negative disease, gemcitabine/carboplatin produced a 34% major response rate; an additional 28% of patients had stable disease > or = 6 months (overall disease control rate, 62%). Gemcitabine/carboplatin/trastuzumab produced an overall response rate of 66%, with a disease control rate of 77%.

A recent multicenter, open-label, randomized, parallel, phase II trial(Xu et al) compared the objective tumor response to biweekly (every 2 weeks) gemcitabine/paclitaxel, gemcitabine/carboplatin, and gemcitabine/cisplatin as first-line treatment for metastatic breast cancer.
The gemcitabine-based treatments had comparable activity and tolerability. Similar survival characteristics and different toxicity profiles suggested that different gemcitabine-platinum may be evaluated further in patients after anthracycline failure.

Xu B, Jiang Z, Kim SB, Yu S, Feng J, Malzyner A, Del Giglio A, Chung HC, Shen LJ, Pen DL.
Biweekly gemcitabine-paclitaxel, gemcitabine-carboplatin, or gemcitabine-cisplatin as first-line treatment in metastatic breast cancer after anthracycline failure: a phase II randomized selection trial.Breast Cancer. 2011 Jul;18(3):203-12
Laessig D, Stemmler HJ, Vehling-Kaiser U, Fasching PA, Melchert F, Kolbl H, Stauch M, Maubach P, Scharl A, Morack G, Meerpohl H, Weber B, Kalischefski B, Heinemann
Gemcitabine and carboplatin in intensively pretreated patients with metastatic breast cancer.

Nagourney, Robert A., Link, John S., Blitzer, Jonathan B., Forsthoff, Cynthia, Evans, Steven S.
Gemcitabine Plus Cisplatin Repeating Doublet Therapy in Previously Treated, Relapsed Breast Cancer Patients
J Clin Oncol 2000 18: 2245-2249

Loesch D, Asmar L, McIntyre K, Doane L, Monticelli M, Paul D, Vukelja S, Orlando M, Vaughn LG, Zhan F, Boehm KA, O’Shaughnessy JA
Phase II trial of gemcitabine/carboplatin (plus trastuzumab in HER2-positive disease) in patients with metastatic breast cancer. Clin Breast Cancer. 2008 Apr;8(2):178-86.

Yardley DA, Burris HA 3rd, Simons L, Spigel DR, Greco FA, Barton JH, Shipley D, Drosick D, Hainsworth JD A phase II trial of gemcitabine/carboplatin with or without trastuzumab in the first-line treatment of patients with metastatic breast cancer. Clin Breast Cancer. 2008 Oct;8(5):425-31