Capecitabine and oxaliplatin in combination as first- or second-line therapy for metastatic breast cancer: a Wisconsin Oncology Network trial

Abstract

Purpose Several cytotoxic chemotherapy regimens are active against metastatic breast cancer; however, benefits are modest and overall prognosis remains limited. For anthracycline and taxane-pretreated metastatic breast cancer, there remains a relative paucity of therapies with significant activity. This Phase II study evaluated the combination of capecitabine and oxaliplatin (XELOX) among patients with metastatic breast cancer being treated in the first or second-line setting. Methods Patients received oxaliplatin 85 mg/m2 on days 1 and 15, and capecitabine 1500 mg/m2 twice daily on days 1-7 and 15-21 of a 28 day cycle. Patients were treated until progression or intolerable toxicity. The primary objective was to estimate the objective response rate by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria with tumor assessments every 8 weeks. Results 10 patients were treated of which 3 had received prior neurotoxic therapy in the metastatic setting. There were no confirmed complete responses, 5 patients had partial response, 4 patients had stable disease for at least 24 weeks, and one patient was unevaluable. Median time to progression (TTP) was 10.4 months (95% lower confidence bound [LCB]: 5.75 months), median progression free survival (PFS) was 14.2 months (95% LCB: 6.14 months), and median overall survival (OS) was 19 months (95% LCB: 12.8 months). Multiple patients experienced pain syndromes and unusual neuropathies. Other common toxicities included fatigue, diarrhea, and nausea. Conclusions XELOX is a promising regimen for anthracycline-pretreated metastatic breast cancer although careful patient selection is indicated and alternate dosing schedules should be explored to minimize neurologic morbidity.

Thermosensitive Liposomes for the Delivery of Gemcitabine and Oxaliplatin to Tumors

“…This drug is used for a number of cancers, but one of its many possible uses is as a second line treatment for breast cancer. 33 Both GEM and OXA are highly water-soluble drugs (>8 mg/mL) with a low cell membrane permeability (<1 × 10 −6 cm/s), and GEM and OXA are taken up by cells via nucleoside transporters 34 and organic cation transporters, 35 respectively. There are several examples of liposomal formulations for delivery of GEM and OXA described in the literature, including long circulating liposomes, 36−39 ligandtargeted liposomes 40 and traditional-TSLs, 41 and recent reviews cover these formulations in more detail.…”

“…30−32 We also investigated the suitability of using a uTSL for the delivery of OXA, a possible second line treatment for breast cancer. 33 Following first-line therapy with anthracycline chemotherapy (DOX etc. ), many patients that show cancer recurrence are not suitable for further treatment with DOX or other drugs that have known cardiotoxicity; hence, drugs such as OXA can be used to obviate this potential toxicity.…”

Trial Watch

“…During the last 13 mo, the clinical profile of oxaliplatin as an off label therapeutic intervention has been assessed in patients with (1) aggressive relapsed or refractory CLL, as part of a chemotherapeutic regimen involving fludarabine, cytarabine (a nucleoside analog approved for the treatment of various hematological malignancies), and rituximab (a CD20-targeting monoclonal antibody currently employed against CLL and NHL); 72 (2) refractory germ cell tumors, in combination with bevacizumab; 73 (3) breast carcinoma, combined with capecitabine (the precursor of 5-fluorouracil) or docetaxel (a microtubular inhibitor of the taxane family currently employed against various carcinomas); 74 , 75 (4) NSCLC, as part of a docetaxel-based chemotherapy; 76 , 77 (5) advanced nasopharyngeal carcinoma, coupled to radiation therapy; 78 (6) gastric or gastresophageal carcinoma, most frequently in the context of a chemotherapeutic cocktail involving docetaxel, capecitabine, or S-1 (an oral fluoropyrimidine currently approved for the treatment of gastric cancer); 79 - 90 (7) pancreatic, gallbladder, or biliary tract tumors, often in combination with gemcitabine-based chemotherapy; 91 - 94 (8) ovarian or bladder carcinoma, combined with conventional (often gemcitabine-based) therapeutic interventions; 95 - 97 or (9) various solid tumors, again in combination with cytotoxic chemotherapy. 98 , 99 Taken together, the results of these clinical trials, most of which were Phase I or II studies, indicate that oxaliplatin exerts promising antineoplastic effects in patients affected by several tumors other than colorectal carcinoma.…”

Correlation of Platinum Cytotoxicity to Drug-DNA Adduct Levels in a Breast Cancer Cell Line Panel

“…Though oxaliplatin is not currently approved for the treatment of breast cancer, it has been shown to be clinically efficacious as a single agent or in combination regimens in breast cancer patients. In metastatic breast cancer patients, oxaliplatin alone had an overall response rate of 21% and in combination therapies had a range of overall response rates from 6.7 to 59% with a median of 31.2%. − In locally advanced breast cancer patients, the overall response rate was even higher at 69% …”