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  • 1
    ISSN: 1569-8041
    Keywords: monotherapy ; non-Hodgkin's lymphoma ; oxaliplatin ; salvage therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Many patients with advanced NHL ultimately relapse and require salvage treatment. Oxaliplatin, a diaminocyclohexane (DACH) platinum, has shown a differential spectrum of cytotoxicity with cisplatin, with activity in primary or secondary cisplatin-resistant solid tumors (colon and ovarian cancer). We report the tolerance/activity of this platinum derivate in previously-treated NHL patients. Patients and methods: From July 1988 to February 1994, 22 patients (11 men, 11 women) with recurrent NHL received single-agent oxaliplatin (100–130 mg /m2 i.v. over two hours with antiemetic premedication, q three weeks). All had been previously treated (median number of prior chemotherapy regimens 2, range 1–7) ≥1 alkylating agent: 22 patients, anthracyclines: 18 patients, cisplatin: four patients, and radiation: 11 patients. Fourteen patients (63%) had progessive disease as best response to their last chemotherapy, and were considered treatment-refractory. All histologies were centrally reviewed in accord with the R.E.A.L. Classification; they were: eight follicular, five MCL, three diffuse large cell, two MALT, one lymphoplasmocytoid, and three other. Results: A total of 144 cycles were administered for a median number of 6 (range 1–30) per patient. The objective response rate was 40% (95% CI: 21–64), including one CR (MCL) and eight PRs (four follicular, two MCL, two MALT). The median response duration was 27 months (range 5–44). Treatment-related toxicity was limited to grade 1–2 nausea/vomiting and reversible grade 1–2 peripheral neuropathy in most of the patients. Conclusion: Oxaliplatin is an active agent in relapsed/refractory NHL, including the MCL type. Its safety profile makes this agent a good candidate for the development of combined salvage regimens. Further phase II studies are needed to confirm these preliminary results.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; efficacy ; oxaliplatin ; platinum compounds ; salvage chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To provide evidence for the therapeutic efficacy of oxaliplatin (Eloxatin®) when given as a 2–6-hour i.v. infusion, alone or in combination with 5-fluorouracil/folinic acid (5-FU ± FA) in patients with advanced colorectal carcinoma (ACRC) who have failed 5-FU-based therapy. To confirm the safety of the drug and its combination in an extended-access context. Patients and methods: Prescribing physicians were supplied oxaliplatin on a nominative compassionate-use basis, after obtaining informed consent. Europe-wide, 206 ACRC patients in 44 centers received 1168 cycles of chemotherapy with oxaliplatin (80–100 mg/m2 q 2 weeks or 100–135 mg/m2 q 3 weeks) delivered as a short (2–6 hours) i.v. infusion, 177 of them (1026 cycles) receiving oxaliplatin + 5-FU ± FA. Results: Oxaliplatin added to the 5-FU ± FA regimens of 111 verified 5-FU-refractory patients (imaging and/or clinical proof of progression under prior 5-FU-based regimen), elicited objective responses in 25 of 98 evaluable patients, (ORR: 25.5%, 95% confidence interval (95% CI: 17–35). The median time to progression was 4.1 months (95% CI: 3.3–5.0) and the median overall survival was 9.6 months (95% CI: 8.2–10.9). Differences in the toxicity profile of the oxaliplatin + 5-FU ± FA combination appear related to administration modality, dose and schedule of the 5-FU-based regimen. Conclusions: The addition of oxaliplatin (2–6-hour i.v. infusion) to 5-FU ± FA regimens is active in ACRC patients with clinical resistance to fluoropyrimidines. The therapeutic index of oxaliplatin + 5-FU ± FA combinations administered as salvage therapy compares favorably with those reported in recent phase II–III trials involving other new agents or combinations active in 5-FU-refractory ACRC patients.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1569-8041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1569-8041
    Keywords: chronotherapy ; colorectal cancer ; liver metastases ; oxaliplatin ; surgery ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Context: Long-term survival of patients with metastatic colorectal cancer has been achieved only in patients who underwent complete resection of metastases. Such surgery could be performed in a greater proportion of patients if effective chemotherapy could downstage previously unresectable metastases. This approach has been limited by the low tumor response rate achieved with conventional chemotherapy. Objective: We studied the outcome of patients with initially unresectable liver metastases from colorectal cancer treated with a three-drug chemotherapy regimen followed by liver metastases surgery whenever possible. Patients and methods: From March 1988 to June 1994, 151 patients with colorectal liver metastases were considered initially unresectable because of large tumor size (〉5 cm), multinodular (〉4) or ill-located metastases. All patients received fully ambulatory chemotherapy with 5-fluorouracil, leucovorin and oxaliplatin (chronotherapy in 83% of them). They were periodically reassessed for surgery by a joint medico-surgical team. Results: In 151 patients, the size of liver metastases decreased by 〉50% in 89 patients (59%) and median overall survival was 24 months (95% confidence interval (95% CI): 19–28 months), with 28% surviving at five years (20%–35%). Surgery with curative intent was attempted in 77 patients (51%), complete resection of liver metastases was achieved in 58 patients (38%). The median survival of the 77 operated patients was 48 months (25–71), with a five-year survival rate of 50% (38–61). Conclusion: This new strategy of combining effective chemotherapy with surgery apparently altered the natural history of unresectable colorectal cancer metastases.
    Type of Medium: Electronic Resource
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