Phase II study of gemcitabine plus cisplatin in metastatic breast cancer

Fuentes, Homero; Calderillo, German; Alexander, Francisco; Ramirez, M.; Avila, Enrique M.; Pérez, L Barrajón; Aguirre, Guillermo; Oñate‐Ocaña, Luis F.; Gallardo, Dolores; Otero, Jorge

doi:10.1097/00001813-200606000-00011

Cited by 17 publications

(17 citation statements)

References 20 publications

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“…Overall, the major hematologic toxicities associated with the combination of gemcitabine and cisplatin have been neutropenia and thrombocytopenia, and the major nonhematologic toxicities have been nausea/vomiting, nephrotoxicity and neurotoxicity [26] . While 6.4% of the patients in our trial developed grade 3/4 neutropenia, no thrombocytopenia was observed.…”

Section: Discussionmentioning

confidence: 99%

Cisplatin plus Gemcitabine Chemotherapy in Taxane/Anthracycline-Resistant Metastatic Breast Cancer

Somali¹,

Alacacıoğlu²,

Tarhan³

et al. 2009

Chemotherapy

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Background: The most commonly used chemotherapeutic regimens in the treatment of metastatic breast cancer (MBC) include anthracyclines and taxanes. In our study, we investigated the efficacy and tolerability of cisplatin plus gemcitabine combination chemotherapy regimen in patients with MBC, who exhibited disease progression after anthracycline- and taxane-based chemotherapy. Methods: Thirty-three patients with taxane/anthracycline-resistant MBC have been treated with gemcitabine 1,000 mg/m² intravenously and cisplatin 30 mg/m² intravenously on days 1 and 8 of a 3-week treatment cycle. Results: Thirty-one patients were assessable for response. One of the 31 patients (3.2%) showed complete response, while 7 patients (22.6%) showed partial response; the objective response rate was 25.8%. Stable and progressive disease was observed in 6 (19.4%) and 17 patients (54.8%), respectively. The median time to progression was 4 months (95% CI 2.15–5.85). The median survival time of all patients was 9.5 months (95% CI 7.86–11.14). Conclusion: Gemcitabine and cisplatin combination therapy is moderately active and safe in patients with MBC previously treated with anthracycline and taxanes.

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Section: Discussionmentioning

confidence: 99%

Cisplatin plus Gemcitabine Chemotherapy in Taxane/Anthracycline-Resistant Metastatic Breast Cancer

Somali¹,

Alacacıoğlu²,

Tarhan³

et al. 2009

Chemotherapy

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“…The combination of gemcitabine and cisplatin was shown to be effective in several trials, inducing response rates between 30 and 52% in patients pretreated with taxanes and/or anthracyclines [6,7,8,9,10]. …”

Section: Introductionmentioning

confidence: 99%

Gemcitabine and Carboplatin in Intensively Pretreated Patients with Metastatic Breast Cancer

et al. 2007

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Background: Patients with metastatic breast cancer (MBC) are increasingly exposed to anthracyclines and taxanes either during treatment of primary breast cancer or during initial therapy of metastatic disease. The combination of gemcitabine and carboplatin was therefore investigated as an anthracycline- and taxane-free treatment option. Patients and Methods: MBC patients previously treated with chemotherapy were enrolled in a multicenter phase II study. Treatment consisted of gemcitabine (1,000 mg/m² i.v. on days 1 and 8) and carboplatin (AUC 4 i.v. on day 1) applied every 3 weeks. Results: Thirty-nine patients were recruited, and a total of 207 treatment cycles were applied with a median of 5 cycles per patient. One complete response and 11 partial responses were observed for an overall response rate of 31% (95% CI: 17–48%). Twelve patients (31%) had stable disease. Median time to progression was 5.3 months (95% CI: 2.6–6.7 months) and median overall survival from start of treatment was 13.2 months (95% CI: 8.7–16.7 months). Grade 3/4 hematological toxicity included leukopenia (59%/5%), thrombocytopenia (26%/23%) and anemia (10%/0%). Nonhematological toxicity was rarely severe. Conclusion: Combination chemotherapy with gemcitabine and carboplatin is an effective and generally well-tolerated treatment option for intensively pretreated patients with MBC. Due to a considerable incidence of severe thrombocytopenia it would be reasonable to consider starting gemcitabine at the lower dose level of 800 mg/m².

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“…Gemcitabine and cisplatin have demonstrated response rates of 29-62% in previously treated advanced breast cancer patients in the phase II setting; however, a high incidence of thrombocytopenia (up to 32%) was observed necessitating gemcitabine dose reduction [14,22,40]. The two responding breast cancer patients in this study were heavily pre-treated with prior chemotherapy but neither had any prior cisplatin, and the patient with a CR did not receive prior gemcitabine.…”

Section: Discussionmentioning

confidence: 74%

A phase I safety, pharmacological, and biological study of the farnesyl protein transferase inhibitor, lonafarnib (SCH 663366), in combination with cisplatin and gemcitabine in patients with advanced solid tumors

Chow

Eckhardt

O’Bryant

et al. 2007

Cancer Chemother Pharmacol

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Purpose-This phase I study was conducted to evaluate the safety, tolerability, pharmacological properties and biological activity of the combination of the lonafarnib, a farnesylproteintransferase (FTPase) inhibitor, with gemcitabine and cisplatin in patients with advanced solid malignancies.Experimental design-This was a single institution study to determine the maximal tolerated dose (MTD) of escalating lonafarnib (75-125 mg po BID) with gemcitabine (750-1,000 mg/m 2 on days 1, 8, 15) and fixed cisplatin (75 mg/m 2 day 1) every 28 days. Due to dose-limiting toxicities (DLTs) of neutropenia and thrombocytopenia in initial patients, these patients were considered "heavily pretreated" and the protocol was amended to limit prior therapy and re-escalate lonafarnib © Springer-Verlag 2007 Correspondence to: Lia Gore, lia.gore@uchsc.edu. NIH Public Access Author ManuscriptCancer Chemother Pharmacol. Author manuscript; available in PMC 2010 January 29. in "less heavily pre-treated patients" on 28-day and 21-day schedules. Cycle 1 and 2 pharmacokinetics (PK), and farnesylation of the HDJ2 chaperone protein and FPTase activity were analyzed.Results-Twenty-two patients received 53 courses of therapy. Nausea, vomiting, and fatigue were frequent in all patients. Severe toxicities were observed in 91% of patients: neutropenia (41%), nausea (36%), thrombocytopenia (32%), anemia (23%) and vomiting (23%). Nine patients withdrew from the study due to toxicity. DLTs of neutropenia, febrile neutropenia, thrombocytopenia, and fatigue limited dose-escalation on the 28-day schedule. The MTD was established as lonafarnib 75 mg BID, gemcitabine 750 mg/m 2 days 1, 8, 15, and cisplatin 75 mg/m 2 in heavily pre-treated patients. The MTD in the less heavily pre-treated patients could not be established on the 28-day schedule as DLTs were observed at the lowest dose level, and dose escalation was not completed on the 21-day schedule due to early study termination by the Sponsor. No PK interactions were observed. FTPase inhibition was not observed at the MTD, however HDJ-2 gel shift was observed in one patient at the 100 mg BID lonafarnib dose. Anti-cancer activity was observed: four patients had stable disease lasting >2 cycles, one subject had a complete response, and another had a partial response, both with metastatic breast cancer. Conclusion-Lonafarnib

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Phase II study of gemcitabine plus cisplatin in metastatic breast cancer

Cited by 17 publications

References 20 publications

Cisplatin plus Gemcitabine Chemotherapy in Taxane/Anthracycline-Resistant Metastatic Breast Cancer

Cisplatin plus Gemcitabine Chemotherapy in Taxane/Anthracycline-Resistant Metastatic Breast Cancer

Gemcitabine and Carboplatin in Intensively Pretreated Patients with Metastatic Breast Cancer

A phase I safety, pharmacological, and biological study of the farnesyl protein transferase inhibitor, lonafarnib (SCH 663366), in combination with cisplatin and gemcitabine in patients with advanced solid tumors

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