Study Of Oxaliplatin In Patients Research Articles

A phase II trial of oxaliplatin in patients with advanced melanoma

18016 Background: Oxaliplatin is a platinum derivative without nephrotoxicity with in vitro activity against human melanoma cell lines. (Mohammed, MQ, 2000; Tashiro, T, 1989). A Phase I trial suggested activity in melanoma (Mathe, G, 1986) but Phase II data is lacking. A non-nephrotoxic platinum compound active in melanoma is of interest in the development of combination chemo-or chemoimmunotherapy. Methods: This was a Phase II prospective study of oxaliplatin in patients with previously treated or refractory advanced melanoma. The primary endpoint was to evaluate the response rate, survival, freedom from progression (FFP) and the tolerability of oxaliplatin in this patient population. Key inclusion criteria were: metastatic (stage IV) or unresectable malignant melanoma progressing following treatment with at least one and at most three chemotherapy regimens. ECOG PS 0–2, measurable disease and adequate organ and marrow function were required. Oxaliplatin 130 mg/m2 was given IV in 250–500 mL D5W over 120 minutes every 21 days for at least 2 cycles. Patients were evaluated for response every 2 cycles. Gehan’s two-stage design was utilized. Results: Ten patients were treated between March 2004 and March 2005. Three patients were female and 3 male with a median age of 62.5 years. All patients had PS 0–1. The median number of cycles was 2 (1–6). Three patients had disease stabilization (SD) for median of 3 months. No objective responses were seen; therefore, the study did not progress to the second stage.All patients have progressed and all have expired but one. Median survival from registration was 168 days (128–383). Toxicities included grade 2 fatigue (2 pts) and grade 2 neuropathy (3 pts); one patient had grade 3 diarrhea. Conclusions: Treatment with oxaliplatin in previously treated patients with melanoma is well tolerated at the dose and schedule studied but did not result in objective responses and further development in this population cannot be recommended. Incorporation into combination regimens in previously untreated patients may be of interest. No significant financial relationships to disclose.

Phase II study of oxaliplatin in patients with recurrent or refractory non‐Hodgkin lymphoma

Oxaliplatin is a platinum derivative with a broad range of anticancer activity. The objective of the current Phase II trial was to investigate the activity of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma (NHL). Patients with recurrent and refractory NHL who received a maximum of 3 previous chemotherapy regimens were considered eligible if they had an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ function. Oxaliplatin was administered in an outpatient setting at a dose of 130 mg/m(2) by 2-hour intravenous infusion every 21 days for < or = 6 cycles in the absence of disease progression. Thirty-one patients (23 with aggressive NHL and 8 with indolent NHL) were enrolled, of whom 30 were assessable for toxicity, response, and survival. The median patient age was 62 years, and 20% of the patients previously received platinum-containing therapy. Eighty-three percent of the patients were refractory to their last treatment regimens. Grade 3 and 4 toxic effects (according to the National Cancer Institute's Common Toxicity Criteria [version 2.0]) included sensory neuropathy (10%), neutropenia (17%), and thrombocytopenia (20%). Objective responses occurred in 8 (27%; 95% confidence interval, 13-47%) of the patients. Responses were observed in platinum-naive patients as well as in those previously treated with platinum. The overall median failure-free survival duration was 3.0 months (range, 0.1-18.1 months). Oxaliplatin had favorable single-agent activity in previously treated patients with refractory lymphoma. The favorable safety profile and the ease of its administration in outpatient settings warrant investigating it in combination with other active drugs for the treatment of recurrent and refractory NHL.

Phase II study of oxaliplatin in patients with unresectable, metastatic or recurrent hepatocellular cancer

4161 Background: Prolonged survival for patients with unresectable HCC has remained elusive, with median overall survival consistently lower than 6 months. Oxaliplatin has recently demonstrated promise in HCC, and the aim of this study is to examine the response rate, survival, time to progression and toxicity in patients with poor prognosis HCC treated with single agent oxaliplatin. Methods: Patients were required to have measurable recurrent, metastatic or unresectable HCC, exposed to no more than 2 prior chemotherapy regimens. Prior radiation, chemoembolization, and/or alcohol injections were permitted. Karnofsky performance of 70% or above and adequate organ and hematologic function were required. All patients (pts) received treatment with oxaliplatin 100 mg/m2 on day 1 and 15 as a two hour IV infusion and were pretreated with antiemetics. Treatment was repeated every 28 days. Results: Thirty four patients have been enrolled and thirty two eligible patients are evaluable for response; there are seventeen Caucasians, three African-American, and fourteen Asians, with 28 males and 6 females. Median age at study entry was 60 years, range (21–84). Karnofsky performance status was 70/80/90/100% in 4/10/7/13 pts; All patients had previous surgery. Among the 32 evaluable pts, one had a PR and twelve had stable disease. Of the remaining 19 patients, 18 had disease progression and 1 had UPR.Overall, median time to progression or death on this study is 2 months; the overall median survival is 6 months. Six month survival is 51% (95% CI 34%–77%) and 6 month event-free survival is 16% (95% CI 6%–42%). Grade III toxicities included neutropenia (2), anemia (1), fatigue (4), transaminitis (8), hyperbilirubinemia (1), elevated alkaline phosphatase (2), hyperglycemia (1), hyponatremia (2), and neuropathy (1). Conclusion: Oxaliplatin as a single agent has demonstrated potential activity in the treatment of poor prognosis HCC, although the majority of patients did not achieve a partial response a significant number had stable disease with a favorable toxicity profile. The combination of oxaliplatin and other agents, may have better efficacy in this patient population. (Supported by CA62505 and N01-CM17101) No significant financial relationships to disclose.

Phase II Study of Oxaliplatin in Patients with Relapsed or Refractory Non-Hodgkin's Lymphoma: Final Results.

Many patients with NHL suffer from refractory or relapsed disease, and platinum-based combination therapy is widely used for salvage therapy. Oxaliplatin, a novel platinum derivative, is a more potent cytotoxic agent than cisplatin, demonstrating greater efficacy against many tumor cell lines, including lymphoma cell lines. Clinical studies of oxaliplatin for other malignancies have shown a favorable toxicity profile. The objective of this phase II trial was to investigate the activity of oxaliplatin in patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). Patients with measurable NHL who had experienced failure of one or more prior chemotherapy regimens were considered eligible. They were required to have an ECOG performance status £ 2 and adequate organ function. Patients were excluded if they had HIV infection, CNS lymphoma, or had chemotherapy or radiotherapy within 4 weeks prior to entering the study. All patients gave their written informed consent to participate. Oxaliplatin was administered at 130 mg/m2 every 21 days for up to six cycles in the absence of progression. Thirty-one patients (23 with aggressive NHL, 8 with indolent NHL) were enrolled on this trial. Thirty eligible patients received oxaliplatin, who were all assessable for toxicity. Response and survival were also analyzed in all 30 patients based on intention to treat analysis. The median patient age was 62 years, and most of the patients had an ECOG performance status of 0 or 1. The most common toxic effect was sensory neuropathy (87%). Grade 3 and 4 toxic effects included sensory neuropathy (10%), neutropenia (17%), and thrombocytopenia (20%). Objective responses occurred in 8 (27%) of the patients: 7 with aggressive NHL, 1 with indolent NHL. The median failure-free survival duration in the entire group, aggressive NHL group and indolent NHL group was 3.0, 2.1 and 4.0 months, respectively. It is noteworthy that three of the five patients with MCL (60%) had a significant response to oxaliplatin, including two CRus, with a median FFS duration of 5 months. When patient group is divided by IPI score (0/1 and 2 /3), the median FFS duration was 3.4 months and 2.6 months, respectively. Median response duration for entire group was 3.0 months. In summary, oxaliplatin has modest activity in patients with previously treated NHL, especially those with aggressive disease. The favorable toxicity profile of oxaliplatin warrants further investigation of it either in combination chemotherapy or with targeted biologic therapy.

Phase II study of oxaliplatin in patients with unresectable, metastatic or recurrent hepatocellular cancer

Phase II study of oxaliplatin in patients with unresectable, metastatic or recurrent hepatocellular cancer

Phase II study of oxaliplatin in patients with unresectable, metastatic or recurrent hepatocellular cancer

4169 Background: Prolonged survival for patients (pts) with unresectable hepatocellular cancer (HCC) has remained elusive, with median overall survival consistently less than 6 months. Oxaliplatin has recently demonstrated promise activity in HCC. The aim of this study is to determine the response rate, survival, time to progression and toxicity in pts with poor prognosis HCC treated with single agent oxaliplatin. Methods: pts were required to have measurable recurrent, metastatic or unresectable HCC, exposed to no more than 2 prior chemotherapy regimens. Prior radiation, chemoembolization, and/or alcohol injections were permitted. Karnofsky performance of 70% or above and adequate organ and hematologic function were required. All patients (pts) received treatment with oxaliplatin 100 mg/m2 on day 1 and 15 as a two hour IV infusion and were pretreated with antiemetics. Treatment was repeated every 28 days. Results: Fifteen pts have been enrolled and fourteen eligible patients are evaluable for response; there are five Caucasians, one African-American, and eight Asians. 12 are males and 2 females. Median age at study entry was 62 years, (range 34–80). Karnofsky performance status was 70/80/90/100% in 1/1/3/9 pts; thirteen pts had previous surgery. Among the 14 evaluable pts, one PR was deserved and six had stable disease. The pt experiencing a PR normalized his AFP; has only a small residual liver mass remaining; and is free of progression at nine months. Median time to progression or death on this study is 2.7 months (mo); the overall median survival is 10 mo. Six mo survival is 51% (95% CI 28%–94%) and 6 mo event-free survival is 29% (95% CI 11%–72%). Five pts died from progressive disease, and one pt died of pneumonia. Grade III toxicities included neutropenia (1), anemia (1), fatigue (2), transaminitis (2), hyperbilirubinemia (1), elevated alkaline phosphatase (1), hyperglycemia (1), hyponatremia (1), and neuropathy (1). Conclusion: Oxaliplatin as a single agent has demonstrated potential activity in the treatment of poor prognosis HCC; accrual to this study will continue past the interim analysis. (Supported by CA62505 and N01-CM17101) No significant financial relationships to disclose.

Oxaliplatin in ovarian cancer

Oxaliplatin in ovarian cancer

Phase I study of oxaliplatin in patients with advanced cancer

Oxaliplatin, or trans-1-diaminocyclohexane-platinum, was tested in a phase I study. A total of 44 patients received 116 courses with dose escalation from 45 to 200 mg/m2. Neither renal nor hematologic toxicities were observed at doses up to 200 mg/m2. Gastrointestinal toxicity was practically constant and often of grade 3-4 on the WHO scale (53% of patients). The dose-limiting toxicity was a peculiar sensory neuropathy; the first neurologic phenomena appeared at a dose of 135 mg/m2 and continued thereafter, occurring after 75% of the courses with mild to moderate intensity (WHO grade 1-2 after 67% of the courses). Neurotoxicity was cumulative and six patients developed grade 3 disabling neuropathy after a cumulative dose of 500 mg/m2, with walking and handwriting difficulties being slowly regressive in three cases. A peculiar symptom was the influence of temperature, with exacerbation of parethesias when patients touched cold surfaces. Nerve-conduction studies carried out in six cases showed a predominantly sensory neuropathy with axonal degeneration. No other toxicities were observed, although audiograms were not systematically done. We observed four partial responses that lasted 6-13 months in patients with oesophageal (2 cases), lung (1), and urothelial cancer (1); two of these patients had been pretreated with cisplatin. Since neurologic side effects occur very frequently and may produce a long-lasting sensory neuropathy, for phase II studies we recommend a starting dose of 135 mg/m2, with a careful neurologic survey.