High-Dose Platinum Combination Therapy in Pretreated Patients with Disseminated Melanoma

Hofmann, Maja; Gabriel, Verena; Milling, Annett; Kiecker, Felix; Sterry, Wolfram; Trefzer, Uwe

doi:10.1159/000110007

Cited by 11 publications

(7 citation statements)

References 57 publications

(33 reference statements)

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“…Nephrotoxicity is one of the major dose-limiting side effects of cisplatin [5][6][7] . Although hydration with saline and use of furosemide can alleviate this effect to some extent [8] , even mild nephrotoxicity is inevitable in most cases and potential kidney-protective agents are needed. Despite the extensive studies on mechanisms of nephrotoxicity, the pathogenesis has not been fully understood.…”

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confidence: 99%

Evaluation of the Effect of Acetyl <i>L</i>-Carnitine on Experimental Cisplatin Nephrotoxicity

Tüfekçi¹,

Güneş²,

Özoğul³

et al. 2009

Chemotherapy

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Background/Aims: To evaluate the protective effects of acetyl L-carnitine (ALCAR) on cisplatin-induced nephrotoxicity in rats, and to gain insights into the possible protective mechanisms of ALCAR against nephrotoxicity. Methods: Twenty-eight Wistar rats were divided into four groups. Group 1 was administered saline only, group 2 was administered ALCAR, group 3 was administered cisplatin, and group 4 was administered ALCAR prior to cisplatin. Rats were sacrificed after 72 h of cisplatin/saline infusion. Serum creatinine and glomerular filtration rate values were obtained, and kidney samples were examined by light and electron microscopy. Apoptotic cell death and caspase-3, 8 and 9 activities were studied immunohistochemically. Results: In group 4, ALCAR administration resulted in an improvement in kidney function tests. Histopathological findings confirmed the biochemical data. Whilst the fusion of the foot processes of podocytes was observed in group 3, they were intact in group 4 on electron-microscopic examination. Apoptotic cell death and caspase-3, 8 and 9 activities were also decreased in group 4 compared to group 3. Conclusions: Antioxidative, antiapoptotic and anti-inflammatory properties of ALCAR were supported by the findings that this agent improves kidney function tests and has the effects of tissue protection and inhibition of apoptosis in cisplatin-induced nephrotoxicity.

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confidence: 99%

Evaluation of the Effect of Acetyl <i>L</i>-Carnitine on Experimental Cisplatin Nephrotoxicity

Tüfekçi¹,

Güneş²,

Özoğul³

et al. 2009

Chemotherapy

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“…Dacarbazine-containing or other combination chemotherapeutic regimens, including the multi-agent Dartmouth regimen (consisting of dacarbazine, cisplatin, carmustine and tamoxifen), are able to induce superior response rates compared with single-agent dacarbazine, but at the prize of increased toxicity, which may explain why this approach does not translate into a significantly higher survival [4,[8][9][10] . Similarly, the combination of dacarbazine or its orally available congener, temozolomide, with immunmodulatory agents such as interleukin-2 and interferon-␣ demonstrates significantly improved response rates and duration; however, at the expense of a more adverse side effect profile and no effect on overall survival [11][12][13][14] .…”

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confidence: 99%

Phase II Trial of Dacarbazine and Thalidomide for the Treatment of Metastatic Melanoma

et al. 2009

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Objective: This phase II study evaluated the efficacy and tolerability of dacarbazine in combination with thalidomide in metastatic melanoma patients. Methods: Chemotherapy-naïve patients with histologically confirmed, measurable metastatic melanoma with no evidence of brain metastases and adequate hematologic and organ function received dacarbazine (1,000 mg/m² i.v. every 3 weeks) and thalidomide (starting dose of 200 mg/day orally at night, escalated every 3 weeks) as tolerated. The primary endpoint was objective tumor response, evaluated after every 3 cycles of treatment. Fifteen patients, age range 29–77 years, were accrued for this study. All had stage IV disease (1 M1a, 5 M1b, 9 M1c). Nine patients had had no prior adjuvant therapy, 6 had received prior immunotherapy. The median number of cycles was 5 (range 1–18), with 8 patients receiving ≥3 cycles. The median thalidomide dose administered was 200 mg/day with a maximum tolerated dose of 400 mg/day. Results: Of the 13 patients evaluable for response, 1 patient had a partial response, 3 patients had stable disease and 9 patients had progressive disease. No complete responses were seen. Two patients were not evaluable for response: 1 withdrew due to toxicity and 1 died of unrelated causes. Grade III neutropenia, thrombocytopenia and nausea were attributed to dacarbazine. Grade III/IV constipation, peripheral neuropathy, fatigue, edema and rash were attributed to thalidomide. Conclusion: The addition of thalidomide to dacarbazine in metastatic melanoma yielded activity insufficient to proceed with additional trials of this combination. Thalidomide dose escalation beyond 200 mg/day was limited by unacceptable toxicity. Therefore, this combination does not warrant further investigation.

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“…The importance of dosage intensification has been demonstrated to be true for alkylating agents [16]- [18], anti-neoplastic antibiotics, such as the taxanes and anthracycline derivatives [18]- [21], nucleic acid antagonists [19]- [25] anti-tumor antibodies [25] and platinum compounds [26] [27]. It has shown to apply to many malignancies such as some sarcomas [16] [31].…”

Section: Resultsmentioning

confidence: 99%

Three Protocols Designed to Individualize and Maximize Anti-Cancer Drug Therapy

Weiss¹,

Stoloff²

2015

JCT

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The role that attaining maximum drug dosage intensity plays in many anti-cancer protocols is a major one, particularly in those protocols that attempt to totally eradicate the neoplasm. A classic approach to facilitate this process utilizes stem cell transplants as well as the use of hematopoetic growth factors. However, problems arise with both allogenic and autologous transplants as well as from the significant variability in drug tolerance between individual patients. With average fixed dose protocols, these problems substantially limit the ability to optimize drug dosage. We attempted to circumvent this difficulty by using low dose continuous infusional therapy of variable duration depending upon the patient's response, together with simultaneous hematopoietic growth factor support. This paper presents our results with three drugs, doxorubicin, ifosphamide, and vinorelbine. With these protocols, we were able to individualize and optimize the amount of drug delivered to each patient, as well as to substantially increase the drug dosage intensity of each of these agents.

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High-Dose Platinum Combination Therapy in Pretreated Patients with Disseminated Melanoma

Cited by 11 publications

References 57 publications

Evaluation of the Effect of Acetyl <i>L</i>-Carnitine on Experimental Cisplatin Nephrotoxicity

Evaluation of the Effect of Acetyl <i>L</i>-Carnitine on Experimental Cisplatin Nephrotoxicity

Phase II Trial of Dacarbazine and Thalidomide for the Treatment of Metastatic Melanoma

Three Protocols Designed to Individualize and Maximize Anti-Cancer Drug Therapy

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