Different from most of the previous studies using light or photons, we use highly charged ions as projectiles to activate proton migration in the smallest saturated and unsaturated hydrocarbon molecules, i.e., CH4 and C2H2. The H3+ formation channel (H3+ + CH+) and isomerization channel (C+ + CH2+), serving as indicators of proton migration, are observed in the fragmentation of CH4 and C2H2 dications. Corresponding kinematical information, i.e., kinetic energy release, is for the first time obtained in the collisions with highly charged ions. In particular, for the C+ + CH2+ channel, a new pathway is identified, which is tentatively attributed to the isomerization on high-lying states of acetylene dication. The kinetic energy release spectra for other two-body breakup channels are also determined and precursor dication states could thus be identified.
Background Triple-negative breast cancer (TNBC) contributes to poor prognosis and there is no established standard chemotherapy this subtype of patients. It has been postulated that related cancers would confer sensitivity to certain cytotoxic agents like cisplatin. Cisplatin and gemcitabine have single-agent activity in metastatic breast cancer and preclinical data support synergy of the combination. The objective of this study was to evaluate doublet with gemcitabine/Cisplatin (GP) as first-line therapy in patients with metastatic TNBC. Material and Methods: This is a prospective single-institutional, open-label, phase II trial. The primary endpoint was progression free survival (PFS). Eligible subjects were aging from 18 to 75 years old, with no prior chemotherpay for MBC, with tumors negative for ER, PR or HER2, with at least one measurable disease according to the RECIST criteria, with ECOG PS of 0–1, and with adequate organ function. All patients received 21-day cycles of gemcitabine 1,000mg/m2 on days 1 and 8 and cisplatin 25 mg/m2 on days 1 through 3. Treatment was continued until disease progression or unacceptable toxicity or up to 8 cycles. (ClinicalTrials.gov number, NCT00601159) Results: A median age was 49 years (range: 29–74 years). 58 patients had received neo/adjuvant chemotherapy (53 patients with anthracycline and/or taxane). The median number of treatment cycles was six (range: 2–8 cycles). In 64 assessable patients, we observed 10 complete response (CR; 15.6%), 30 partial responses (PR; 46.9%), 17 patients (26.6%) with stable disease (SD), and 7 patients (10.9%) with progressive disease, for an overall response rate of 62.5% (95% CI, 50.3% to 74.7%)..*** The median PFS was 7.7 months (95% CI, 6.0 to 9.4). With a median follow-up time of 28 months, the median overall survival was 19.1 months (95% CI, 12.5 to 25.7). Grade 3 or 4 toxicities were neutropenia 42.2%, thrombocytopenia 29.7%, anemia 18.8%, nausea/vomiting 15.6%, fatigue 14.1%, constipation 3%, sensory neuropathy 1.6%, 2 patients developed febrile neutropenia. The chemotherapy doses were reduced in 13.3% (6 pts) because of toxicity. There were no treatment-related deaths. Conclusion: Significant activity and favorable toxicity profile of GP regimen as first-line chemotherapy in patients with metastatic TNBC. It provided a basis for considering GP for further evaluation in phase III trials for women with metastatic TNBC in China. (ClinicalTrials. gov number, NCT01287624) Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-19-06.
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