Gemcitabine Reverses Cisplatin Resistance: Demonstration of Activity in Platinum- and Multidrug-Resistant Ovarian and Peritoneal Carcinoma

Rose, Peter G.; Mossbruger, Kim; Fusco, Nancy; Smrekar, Mary; Eaton, Susan; Rodriguez, Michael J.

doi:10.1006/gyno.2002.6850

Cited by 102 publications

(68 citation statements)

References 19 publications

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“…The drug has synergistic activity with platinum by forming platinum-DNA adduct which inhibits ribonucleotide reductase. Several clinical studies have demonstrated high efficacy of the combined drugs: RRs of 16-70% with cisplatin (Nagourney et al, 2003;Rose et al, 2003;Brewer et al, 2006;Bozas et al, 2007), 40% with paclitaxel (Garcia et al, 2004;Poole et al, 2006), 13-64% with topotecan (Greggi et al, 2001;Sehouli et al, 2002), or 34% with PLD (Ferrandina et al, 2005). Our study could not demonstrate any RR by a combination regimen in platinum-resistant patients except one patient who could achieve SD.…”

Section: Discussioncontrasting

confidence: 52%

“…Third was the regimen of gemcitabine. Some studies found RRs of 6-29% from single agent (Shapiro et al, 1996;Friedlander et al, 1998;D'Agostino et al, 2003;Markman et al, 2003;Mutch et al, 2007;Ferrandina et al, 2008;Watanabe et al, 2008;Suprasert et al, 2012;Yoshino et al, 2012) while others could demonstrate RRs of 13-70% from gemcitabine in combination with platinum or other agents (Greggi et al, 2001;Sehouli et al, 2002;Nagourney et al, 2003;Rose et al, 2003;Garcia et al, 2004;Papadimitriou et al, 2004;Ferrandina et al, 2005;Brewer et al, 2006;Pfisterer et al, 2006;Poole et al, 2006;Bozas et al, 2007). Another reason which might be under-recognized was the setting when gemcitabine was used or numbers of prior chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Gemcitabine was also tested with other drugs as a combination regimen e.g. cisplatin (Nagourney et al, 2003;Rose et al, 2003;Brewer et al, 2006;Bozas et al, 2007) or carboplatin (Papadimitriou et al, 2004;Pfisterer et al, 2006), PLD (Ferrandina et al, 2005), paclitaxel (Garcia et al, 2004;Poole et al, 2006), topotecan (Greggi et al, 2001;Sehouli et al, 2002), producing high RRs of 13-70% (Greggi et al, 2001;Sehouli et al, 2002;Nagourney et al, 2003;Rose et al, 2003;Garcia et al, 2004;Papadimitriou et al, 2004;Ferrandina et al, 2005;Brewer et al, 2006;Pfisterer et al, 2006;Poole et al, 2006;Bozas et al, 2007).…”

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confidence: 99%

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Treatment Outcomes of Gemcitabine in Refractory or Recurrent Epithelial Ovarian Cancer Patients

Chanpanitkitchot

Tangjitgamol²,

Khunnarong³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: To study the response rate (RR), progression-free survival (PFS) and toxicity profiles of recurrent epithelial ovarian cancer (EOC) patients treated with gemcitabine. Materials and Methods: Recurrent EOC patients who were treated with gemcitabine between January 2000 and December 2013 at the Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital were identified and medical records were reviewed. Clinico-pathological features including data of gemcitabine treatment, response and toxicity were collected. Results: We identified 43 EOC patients who had gemcitabine treatment. All except one patient who did not receive any adjuvant treatment, had received platinum-based chemotherapy. Among these 42 patients, 31.0% had refractory cancer to first-line chemotherapy while 69.0% had recurrence with 48.8% being platinumsensitive. The total cycles of gemcitabine used were 203 (median 4, range 2-9 cycles). Overall RR was 11.6%: 19% in platinum-sensitive vs 4.5% in platinum-resistant groups (p=0.158) and 42.9% in the patients having gemcitabine together with platinum vs 5.6% using gemcitabine alone (P=0.024). Median PFS was 3.6 months (95% confidence interval [CI], 2.73-4.49 months): 8.1 months (95% CI, 2.73-4.49 months) in combination regimen vs 3.2 months (95% CI, 2.01-4.42 months) in single regimen (p=0.077) and 8.1 months (95% CI, 4.73-11.48 months) with the gemcitabine combination vs 2.7 months (95% CI, 1.98-3.38 months) by single gemcitabine in platinum sensitive patients (P=0.007). Common toxicities were hematologic which were well tolerated and manageable. Conclusions: Gemcitabine has modest activity in pre-treated EOC. A combination regimen had higher activity than single agent in platinum sensitive patients with a significant improvement in RR and PFS.

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Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Treatment Outcomes of Gemcitabine in Refractory or Recurrent Epithelial Ovarian Cancer Patients

Chanpanitkitchot

Tangjitgamol²,

Khunnarong³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…In addition, gemcitabine has self-potentiating mechanisms that lead to prolonged high intracellular concentrations of the active metabolites [59]. Although the GOG piloted a study of single-agent gemcitabine in advanced cervical cancer (GOG-127K), which yielded a poor overall response rate of 8% (Table 2) [37], in vitro [60] and in vivo studies in patients with advanced ovarian cancer [61] and advanced pancreatic can- cer [62] have demonstrated synergy between gemcitabine and cisplatin.…”

Section: Protocol 204mentioning

confidence: 99%

Gynecologic oncology group trials of chemotherapy for metastatic and recurrent cervical cancer

Tewari

Monk

2005

Curr Oncol Rep

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“…Given their synergism, absence of significant overlapping toxicities and non-cross-resistance with other regimens, gemcitabine in combination with cisplatin, presents an attractive treatment option. Furthermore, treatment with gemcitabine and cisplatin have been shown to induce responses in patients with ovarian carcinoma previously resistant to cisplatin or gemcitabine (Rose et al, 2003). We previously reported a RR of 80% with GEM-P in 20 patients with relapsed and refractory lymphoma, having met our target of excluding a lower RR of 20% (Chau et al, 2003).…”

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confidence: 94%

Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma

Waters

Cunningham

et al. 2005

Br J Cancer

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There is currently no standard salvage chemotherapy regimen in relapsed and refractory lymphoma. Gemcitabine is a novel nucleoside analogue, which acts synergistically with cisplatin both in vitro and in clinical studies. We evaluated the combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) in 41 heavily pretreated patients with relapsed and refractory Hodgkin's and non-Hodgkin's lymphoma. The best-achieved response rate (RR) was 79% (95% CI 64 -91), with a complete RR of 21%. In patients with chemo-resistant disease, the RR was 63%. Myelosuppression was the main toxicity, the incidence of Grade 3 or 4 anaemia, neutropenia and thrombocytopenia was 17.1, 61.0 and 53.7% respectively. Only one patient had neutropenic sepsis and none of the patients suffered from haemorrhage. Grade 3 or 4 nonhaematological toxicity was minimal and stem cell mobilisation was not inhibited. GEM-P is an effective salvage regimen and its use prior to autologous stem cell transplant warrants further investigation.

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Gemcitabine Reverses Cisplatin Resistance: Demonstration of Activity in Platinum- and Multidrug-Resistant Ovarian and Peritoneal Carcinoma

Cited by 102 publications

References 19 publications

Treatment Outcomes of Gemcitabine in Refractory or Recurrent Epithelial Ovarian Cancer Patients

Treatment Outcomes of Gemcitabine in Refractory or Recurrent Epithelial Ovarian Cancer Patients

Gynecologic oncology group trials of chemotherapy for metastatic and recurrent cervical cancer

Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma

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