Cisplatin improves antitumor activity of weekly nab-paclitaxel in patients with metastatic breast cancer

Abstract

Although nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is approved to be given every 3 weeks, weekly use of this drug is becoming a new standard of care in patients with metastatic breast cancer (MBC). This prospective Phase II study was conducted to improve the efficacy of weekly nab-paclitaxel with cisplatin in MBC patients. Seventy-three women with recurrent or MBC were eligible for participation. Nab-paclitaxel was administered weekly at a dose of 125 mg/m 2 on day 1, day 8, and day 15, followed by cisplatin 75 mg/m 2 on day 1, repeated every 28 days with a maximum of 6 cycles. The primary objective was investigator-assessed overall response rate (ORR). A high ORR of 67.1% was obtained, with rates of 80.6% for the first-line patients and 80% for patients not pretreated with taxanes. Among those who had objective responses, a large percentage of patients (83.7%) showed quickly remarkable tumor shrinkage during the first two cycles. The median progression-free and overall survival times were 9.8 and 26.9 months, respectively. For the patients receiving first-, second-, and third-line therapy or beyond, median progression-free survival was 11.7, 7.7, and 7.6 months, respectively ( P =0.005). Molecular subtype was not significantly associated with ORR or disease progression. Grade 4 neutropenia occurred in 46 patients (63.0%), with febrile neutropenia found in 9 patients (12.3%). Grade 3 peripheral neuropathy was an accumulated dose-limiting toxicity occurring in 19 patients (26.0%). Efficacy of weekly nab-paclitaxel can be improved by adding cisplatin. The doublet is highly effective, with quick response, manageable toxicity, and possible equivalence across molecular subtypes in MBC patients.

Intermittent high dose proton pump inhibitor enhances the antitumor effects of chemotherapy in metastatic breast cancer

“…Cisplatin is moderately active as first-line treatments in MBC, with an objective response rate (ORR) 40 to 60 % [ 50 ]. Cisplatin-based regimens are also widely tested in the first-line metastatic setting with median time to progression (TTP) of 7.2 to 11.7 months and acceptable toxicities [ 51 – 56 ]. Based on these data and sufficient experience of our center [ 56 – 58 ], the doublet TP regimen (docetaxel and cisplatin combination) was an acceptable option for the control arm and suitable for this proof of concept setting.…”

“…Cisplatin-based regimens are also widely tested in the first-line metastatic setting with median time to progression (TTP) of 7.2 to 11.7 months and acceptable toxicities [ 51 – 56 ]. Based on these data and sufficient experience of our center [ 56 – 58 ], the doublet TP regimen (docetaxel and cisplatin combination) was an acceptable option for the control arm and suitable for this proof of concept setting. In the setup of the treatment combining the TP regimen with ESOM we use 3 key criteria: (i) two fixed doses of 160 and 200 mg/day were established based on the pre-clinical evidence of ESOM [ 18 ]; (ii) pretreatment with ESOM, based on the pre-clinical evidence that only pre-treatment showed to increase chemosensitization [ 15 ]; and (iii) the intermittent schedule, based both on the rationale that an acidic pH is needed for a full PPI activation, in order to be transformed into the active molecule (sulfonamide) and on the in vivo evidence showing that tumor pHe is PPI-dependent, showing displayed an initial shift towards neutrality after ESOM treatment, returning to acidic values within 48 h after the stop of the treatment [ 18 ]; we thus used a weekly treatment schedule of consecutive 3 days of a full ESOM dosage, followed by 4 days ESOM off immediately followed by TP regimen-based chemotherapy.…”

DCE-MRI-Derived Parameters in Evaluating Abraxane-Induced Early Vascular Response and the Effectiveness of Its Synergistic Interaction with Cisplatin

“…To further improve the efficacy of weekly Abraxane in advanced (metastatic) cancer patients, combinations of Abraxane with other chemotherapeutic agents or biologics have been tested in several clinical studies [ 3 ]. These clinical trials showed that the combination of Abraxane and carboplatin or cisplatin has better short-term efficacy, a rapid therapy response, and manageable toxicity in breast cancer and lung squamous carcinoma [ 5 , 6 ].…”

Caveolin-1 expression predicts efficacy of weekly nab-paclitaxel plus gemcitabine for metastatic breast cancer in the phase II clinical trial

“…On the other hand, in our previous study, we identified a highly effective doublet of nab-paclitaxel and cisplatin in different lines of metastatic breast cancer patients. An enhanced efficacy was observed with ORR of 67.1%, mPFS of 9.8 months and OS of 26.9 months in 73 enrolled patients [ 13 ]. These findings can serve as a powerful evidence to show the extraordinary antitumor effects of weekly nab-paclitaxel.…”