Schedule-dependent antagonism of paclitaxel and cisplatin in human gastric and ovarian carcinoma cell Lines in vitro

Vanhoefer, U.; Harstrick, A.; Wilke, H.; Schleucher, N.; Walles, Heike; Schröder, J; Seeber, S.

doi:10.1016/0959-8049(94)00440-g

Cited by 54 publications

(37 citation statements)

References 15 publications

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“…Especially, paclitaxel appears to have a schedule-dependent synergy with platinum compounds, as documented in established human gastric cancer cell lines [25]. This synergy has led to the development of paclitaxelplatinum combination regimens in a number of solid tumors, including gastric cancer.…”

Section: Administration Of Paclitaxel Every 3 Weeks (3-weekly)mentioning

confidence: 99%

Paclitaxel chemotherapy for the treatment of gastric cancer

2009

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cause of cancer mortality. Although the incidence of gastric cancer has been declining in most developed countries, esophago-gastric junctional tumor and tumor in the cardia has, conversely, been increasing [2] and these tumors still remain one of the biggest problems worldwide.The prognosis of patients with advanced (i.e., unresectable or metastatic) gastric cancer is very poor. The median survival time for such patients is 6 to 9 months [3]. For many years, various chemotherapeutic agents have been used in attempts to improve survival, progression free-survival, response rate, and quality of life in patients with advanced gastric cancer as well as to improve disease-free survival in patients in whom curative resection of the cancers has been performed. 5-Fluorouracil (5-FU) and cisplatin-based regimens have long been considered reference treatments. Commonly used regimens have included epirubicin, cisplatin, and continuous infusion of 5-FU; 5 days' infusion of 5-FU plus cisplatin every 4 weeks; a weekly infusion regimen of 5-FU/leucovorin (LV) over 24 h plus cisplatin every 2 weeks; and 5-FU bolus plus 22-h infusion of 5-FU on days 1 and 2, in combination with cisplatin every 2 weeks. The results with these regimens, together with other study results, suggested that combination regimens including fl uorinated pyrimidines, cisplatin, doxorubicin, epirubicin, and methotrexate, had better response rates than single agents. Although gastric cancer is a relatively chemosensitive disease, with response rates of 30% to 40%, these treatments have shown a modest but unsatisfactory increase in overall survival [4]. In this regard, chemotherapy in the advanced gastric cancer setting is limited by a low complete response rate, response durations that are shortlived, and considerable toxicities.Nevertheless, recently, the development of new chemotherapeutic and molecular targeting agents has opened the door to various clinical trials to fi nd novel therapeutic strategies to improve the outcome of Abstract A comprehensive review of phase I and phase II clinical trials of paclitaxel and paclitaxel-containing chemotherapy regimens for advanced gastric cancer was performed. Response rates, median progression-free survivals, and median overall survivals were examined, together with the treatment regimens and the numbers of patients registered in each trial. Although paclitaxel monotherapy produced considerable improvement in tumor response and prognosis, combination doublet or triplet chemotherapy with fl uoropyrimidines and/ or platinum compounds showed better results than the paclitaxel monotherapy. With regard to the schedule of paclitaxel administration, weekly injection seemed to show less toxicity and better results than administration every 3 weeks. Adjuvant therapies, chemoradiation therapies, and paclitaxel treatment for gastric ascites were also investigated and are discussed.

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Section: Administration Of Paclitaxel Every 3 Weeks (3-weekly)mentioning

confidence: 99%

Paclitaxel chemotherapy for the treatment of gastric cancer

2009

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“…Paclitaxel exhibits an antitumour activity against various tumours including gastric cancer cell lines (Vanhoefer et al, 1995;Chang et al, 1996). Ajani et al obtained a 17% response rate using paclitaxel as a single agent in gastric cancer, with a tendency towards a higher response rate in patients receiving paclitaxel as continuous infusion over 24 hours.…”

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A phase II study of paclitaxel, weekly, 24-hour continuous infusion 5-fluorouracil, folinic acid and cisplatin in patients with advanced gastric cancer

et al. 2000

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SummaryTo evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel, cisplatin and 24 h continuous infusion of 5-FU/folinic acid in patients (pts) with unresectable, locally advanced or metastatic gastric adenocarcinoma. Forty-five chemotherapy-naive pts (28 male and 17 female) with a median age of 60 years (range 35-74) were enrolled. 5-FU 2 g/m 2 was given weekly over 24 h i.v. preceded by folinic acid 500 mg/m 2 as a 2 h infusion. Paclitaxel 175 mg/m 2 was administered as a 3 h-infusion on days 1 and 22 and cisplatin 50 mg/m 2 as 1 h infusion on days 8 and 29. Six weeks of therapy (days 1, 8, 15, 22, 29, 36) followed by 2 weeks rest were considered one cycle. A median of 3 cycles (range 1-4) were administered to 45 pts assessable for response, survival and toxicity. Five pts (11%) obtained a CR and 18 pts (40%) a PR (ORR 51%; 95% Cl: 35.8-66.3%). Responses were achieved in the liver, lymph nodes, lungs and at the site of the primary tumour. Nine pts (20%) had stable disease. Thirteen pts (29%) were considered to have failed treatment, 8 pts (18%) due to progressive disease and 5 pts (11%) who did not receive one complete cycle of therapy due to acute non-haematologic toxicity. The median progression-free and overall survival times were 9 months (range 1-36+) and 14 months (range 2-36+), respectively. Neutropenia WHO III°/IV°occurred in 7 pts (15%) with only 1 pt having grade IV. Additional non-haematologic WHO III°/IV°toxicities included nausea/vomiting in 5 (11%), alopecia in 22 (49%), and diarrhoea in 1 patient each (2%). Dose reductions or treatment delays were necessary in 8 pts (17%), mainly due to neutropenia. All pts were treated on an outpatient basis. The combination of paclitaxel, cisplatin and continuously infused 5-FU/folinic acid appears to be a highly active regimen for the treatment of pts with advanced gastric cancer. While the overall acceptable toxicity allows its use in the palliative setting, it may also be an attractive option to be tested for neoadjuvant or adjuvant treatment.

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“…A rational step would be to combine paclitaxel with cisplatin, the most active agent in ovarian cancer. In vitro, this combination has demonstrated marked synergism (Untch et al, 1994) in a sequence-dependent way (Jekunen et al, 1994;Vanhoefer et al, 1995). Recently, improved response rates, diseasefree survival and overall survival were demonstrated after paclitaxel and cisplatin combination therapy in first-line treatment for ovarian cancer compared with cisplatin and cyclophoshamide (McGuire et al, 1996).…”

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confidence: 99%

Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer: a feasibility study

Veldhuis

Willemse²,

Beijnen³

et al. 1997

Br J Cancer

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Summary The tolerability and efficacy of four courses of paclitaxel and ifosfamide plus cisplatin every 3 weeks was evaluated in patients with residual or refractory ovarian cancer. Additionally, supportive haematological effects of recombinant human interleukin 3 (rhlL-3) and recombinant human granulocyte colony-stimulating factor (G-CSF) were studied. Paclitaxel starting dose was 135 mg m-2 (day 1), with ifosfamide dose 1.2 g m-2 day-1 (days 2-4) and cisplatin dose 30 mg m-2 day-1 (days 2-4). All 16 patients received 5.0 9g kg-1 day-' G-CSF (days 7-16) and, in addition, eight patients were randomized to receive 10 gg kg-' day-' rhlL-3 (days 5-9). Paclitaxel and ifosfamide doses were reduced when grade IV haematological toxicity occurred. In the absence of grade IV haematological toxicity and normal recovery of haematopoiesis, paclitaxel dose was escalated. Toxicity was evaluable in 56 courses, with haematological effects in 52. Despite antiemetic treatment, nausea and vomiting (2 grade 1) occurred in 50 courses. Five patients had persisting peripheral neuropathy. Renal and liver function were not affected. Grade IV neutropenia occurred in 12 out of 52 courses, with neutropenic fever in two patients, both of whom died from fatal septicaemia. Grade IV thrombocytopenia without bleeding was observed in 15 courses. Grade IV haematological toxicity was associated with hepatic metastases and concurrent increases in alkaline phosphatase (P <0.001) and gamma-glutamyltransferase (P=0.007). No relation was found between haematological toxicity and pharmacokinetic parameters of paclitaxel. Patients treated with rhlL-3 showed a tendency to a faster platelet recovery (not affecting platelet nadir), and the cisplatin dose intensity was higher (P=0.025). Six of the nine evaluable patients had a tumour response. The overall median progression-free survival was 7 months and the overall mean survival was 13 months. In conclusion, this potentially interesting combination as second-line treatment showed a low tolerability with unexpected mortality, while rhlL-3 administration tended to induce a more rapid platelet recovery.

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Schedule-dependent antagonism of paclitaxel and cisplatin in human gastric and ovarian carcinoma cell Lines in vitro

Cited by 54 publications

References 15 publications

Paclitaxel chemotherapy for the treatment of gastric cancer

Paclitaxel chemotherapy for the treatment of gastric cancer

A phase II study of paclitaxel, weekly, 24-hour continuous infusion 5-fluorouracil, folinic acid and cisplatin in patients with advanced gastric cancer

Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer: a feasibility study

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