Activity of Oxaliplatin in Patients With Relapsed or Cisplatin-Refractory Germ Cell Cancer: A Study of the German Testicular Cancer Study Group

Kollmannsberger, Christian; Rick, Oliver; Derigs, HG; Schleucher, N.; Schöffski, Patrick; Beyer, Jörg; Schoch, Robert; Sayer, Herbert G.; Gerl, Arthur; Kuczyk, Markus A.; Spott, C; Kanz, Lothar; Bokemeyer, Carsten

doi:10.1200/jco.2002.08.050

Cited by 94 publications

(37 citation statements)

References 30 publications

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“…The clinical evidence that oxaliplatin is active against cisplatin resistant cancers involves reports of oxaliplatin having greater activity against platinum pre-treated testicular cancer when combined with other chemotherapeutics such as gemcitabine [12,13] or irrinotecan [14] rather than oxaliplatin as a single agent [15]. In these studies it is difficult to determine whether it is the oxaliplatin or the combination of drugs that produces a response in cisplatin pre-treated patients.…”

Section: Introductionmentioning

confidence: 92%

Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells

Stordal

Davey

2005

Cancer Chemother Pharmacol

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Cisplatin produces good responses in solid tumours including small cell lung cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin is reported to show activity against some cisplatin-resistant cancers but there is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin resistant SCLC cell lines.Studies of drug resistance mainly focus on the cellular resistance mechanisms rather than how the cells develop resistance. This study examines the development of cisplatin and oxaliplatin resistance in H69 human SCLC cells in response to repeated treatment with clinically relevant doses of cisplatin or oxaliplatin for either 4 days or 2h. Treatments with 200ng/ml cisplatin or 400ng/ml oxaliplatin for 4 days produced sublines (H69CIS200 and H69OX400 respectively) that showed low level (approximately 2-fold) resistance after 8 treatments. Treatments with 1000ng/ml cisplatin or 2000ng/ml oxaliplatin for 2h also produced sublines, however these were not stably resistant suggesting shorter treatment pulses of drug may be more effective. Cells survived the first five treatments without any increase in resistance, by arresting their growth for a period and then regrowing. The period of growth arrest was reduced after the sixth treatment and the H69CIS200 and H69OX400 sublines showed a reduced growth arrest in response to cisplatin and oxaliplatin treatment suggesting that "regrowth resistance" initially protected against drug treatment and this was further upregulated and became part of the resistance phenotype of these sublines. Oxaliplatin dose escalation produced more surviving sublines than cisplatin dose escalation but neither set of sublines were associated with increased resistance as determined by 5-day cytotoxicity assays, also suggesting the involvement of regrowth resistance. The resistant sublines showed no change in platinum accumulation or glutathione levels even though the H69OX400 subline was more sensitive to buthionine sulfoximine treatment. The H69CIS200 cells were cross-resistant to oxaliplatin demonstrating that oxaliplatin does not have activity against low level cisplatin resistance. Relative to the H69 cells, the H69CIS200 and H69OX400 sublines were more sensitive to paclitaxel and taxotere suggests the taxanes may be useful in the treatment of platinum resistant SCLC. These novel cellular models 3 of cisplatin and oxaliplatin resistant SCLC will be useful in developing strategies to treat platinum-resistant SCLC.

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Section: Introductionmentioning

confidence: 92%

Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells

Stordal

Davey

2005

Cancer Chemother Pharmacol

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“…Thirty-two patients with nonseminomatous, cisplatin-refractory GCTs or relapsed disease after HDCT plus autologous stem cell support were treated with single-agent oxaliplatin [22]. Overall, four patients (13%) achieved a partial remission, and two additional patients achieved disease stabilization (Table 2).…”

Section: Oxaliplatin-based Regimensmentioning

confidence: 99%

Management of Recurrent Testicular Germ Cell Tumors

2007

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LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Discuss the different salvage conventional and high-dose chemotherapy regimens for germ cell tumors.2. List the prognostic factors for recurrent germ cell tumors.3. Explain the role of surgical salvage therapy for recurrent germ cell tumors.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTAlthough front-line chemotherapy cures most men with testicular germ cell tumors, salvage therapy is still important in a small but significant minority. Second-line conventional-dose or high-dose chemotherapy with stem cell rescue may cure 25%-50% of patients. New chemotherapeutic agents, including the taxanes gemcitabine and oxaliplatin, have added to the therapeutic armamentarium. Salvage surgical resection has an important role in selected patients. Cisplatin-refractory patients have a poor prognosis with current therapy, and novel chemotherapeutic and biologic agents need to be discovered for such patients. The Oncologist 2007;12:51-61

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“…Compared with cisplatin, oxaliplatin appears to have a better safety profile; and the cross-resistance to cisplatin is minimal (Kollmannsberger et al, 2002). Oxaliplatin has higher anticancer activity than cisplatin in some preclinical experiments (Di Francesco et al, 2002).…”

mentioning

confidence: 99%

Phase II study of weekly oxaliplatin and 24-h infusion of high-dose 5-fluorouracil and folinic acid in the treatment of advanced gastric cancer

et al. 2004

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To investigate the efficacy and safety of combining weekly oxaliplatin with weekly 24-h infusion of high-dose 5-fluorouracil (5-FU) and folinic acid (FA) in treatment of patients with advanced gastric cancer. Patients with histologically confirmed, locally advanced or recurrent/metastatic gastric cancer were studied. Oxaliplatin 65 mg m À2 2-h intravenous infusion, and 5-FU 2600 mg m À2 plus FA 300 mg m À2 24-h intravenous infusion, were given on days 1 and 8, repeated every 3 weeks. Between January 2001 through January 2002, 55 patients were enrolled. The median age was 64 years (range: 22 -75). In all, 52 patients (94.5%) had recurrent or metastatic disease and three patients had locally advanced disease. Among 50 patients evaluable for tumour response, 28 patients achieved partial response, with an overall response rate of 56% (95% confidence interval (CI): 41.8 -70.3%). All 55 patients were evaluated for survival and toxicities. Median time to progression and overall survival were 5.2 and 10.0 months, respectively, during median followup time of 24.0 months. Major grades 3 -4 toxicities were neutropenia in 23 cycles (7.1%) and thrombocytopenia in 16 cycles (5.0%). Treatment was discontinued for treatment-related toxicities in nine patients (16.4%), of whom eight were due to oxaliplatin-related neurotoxicity. One patient (1.8%) died of neutropenic sepsis. This oxaliplatin-containing regimen is effective in the treatment of advanced gastric cancer. Except for neurotoxicity that often develops after prolonged use of oxaliplatin, the regimen is well tolerated.

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Activity of Oxaliplatin in Patients With Relapsed or Cisplatin-Refractory Germ Cell Cancer: A Study of the German Testicular Cancer Study Group

Cited by 94 publications

References 30 publications

Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells

Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells

Management of Recurrent Testicular Germ Cell Tumors

Phase II study of weekly oxaliplatin and 24-h infusion of high-dose 5-fluorouracil and folinic acid in the treatment of advanced gastric cancer

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