Treatment of uveal melanoma metastatic to the liver. A review of the M.D. Anderson Cancer Center experience and prognostic factors

Bedikian, A. Y.; Legha, S S; Mavligit, G. M.; Carrasco, C. H.; Khorana, Sangeeta; Plager, Carl; Papadopoulos, N; Benjamin, R. S.

doi:10.1016/s0002-9394(14)70300-9

Cited by 34 publications

(58 citation statements)

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“…Although the sensitivity of the melanomas to treosulfan was reduced (Table 2), examination of the individual data shows that most tumours (Table 3) did exhibit some sensitivity to this agent, which remains the best of the alkylating agents we have tried in the assay. We have previously shown that these tumours are relatively unresponsive to temozolomide (Myatt et al, 1997), a drug closely related to dacarbazine (DTIC) which forms the mainstay of treatment for cutaneous melanoma, but has poor results against uveal melanoma (Bedikian et al, 1995). Results for other agents were similar to those obtained previously, with confirmation of some sensitivity of uveal melanoma to paclitaxel, cytosine arabinoside and anthracyclines.…”

Section: Chemotherapy For Choroidal Melanoma 1491supporting

confidence: 72%

“…Choroidal melanoma is a chemoresistant tumour which is fatal in about 50% cases at 10 years and has a median survival of 5 to 7 months following the development of metastases (Ravio, 1977;Albert et al, 1992;Bedikian et al, 1995). Although a high-risk group can be defined by stage (tumour size) and microvascularity , no adjuvant therapy is available for routine use.…”

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confidence: 99%

“…While occasional responses have been reported, there are few trial-based data from which response rates can be obtained (Albert et al, 1992). One large series reported a response rate less than 1% for systemic therapy, although chemoembolization of the liver using cisplatin-based regimens was more effective, producing responses in 36% of patients (Cantore et al, 1994;Bedikian et al, 1995). The results of these studies suggest that at least some of these tumours are partially sensitive to platinum-based therapy, although in systemic combination with other drugs, cisplatin shows little effect (Proebstle et al, 1996).…”

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confidence: 99%

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Combination chemotherapy for choroidal melanoma: ex vivo sensitivity to treosulfan with gemcitabine or Cytosine arabinoside

et al. 1999

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Summary Treatment of choroidal melanoma by chemotherapy is usually unsuccessful, with response rates of less than 1% reported for dacarbazine (DTIC)-containing regimens which show 20% or more response rates in skin melanoma. Recently, we reported the activity of several cytotoxic agents against primary choroidal melanoma in an ATP-based tumour chemosensitivity assay (ATP-TCA). In this study, we have used the same method to examine the sensitivity of choroidal melanoma to combinations suggested by our earlier study. Tumour material from 36 enucleated eyes was tested against a battery of single agents and combinations which showed some activity in the previous study. The combination of treosulfan with gemcitabine or cytosine arabinoside showed consistent activity in 70% and 86% of cases, respectively. Paclitaxel was also active, particularly in combination with treosulfan (47%) or mitoxantrone (33%). Addition of paclitaxel to the combination of treosulfan + cytosine analogue added little increased sensitivity. For treosulfan + cytosine arabinoside, further sequence and timing experiments showed that simultaneous administration gave the greatest suppression, with minor loss of inhibition if the cytosine analogue was given 24 h after the treosulfan. Administration of cytosine analogue 24 h before treosulfan produced considerably less inhibition at any concentration. While we have so far been unable to study metastatic tumour from choroidal melanoma patients, the combination of treosulfan with gemcitabine or cytosine arabinoside shows activity ex vivo against primary tumour tissue. Clinical trials are in progress.

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Section: Chemotherapy For Choroidal Melanoma 1491supporting

confidence: 72%

mentioning

confidence: 99%

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confidence: 99%

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Combination chemotherapy for choroidal melanoma: ex vivo sensitivity to treosulfan with gemcitabine or Cytosine arabinoside

et al. 1999

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“…Notable success has been also achieved with embolization of ocular melanomas to the liver [2]. Other liver metastases, such as from the breast, lung, kidney, bladder, and-pancreas, and gastrointestinal sarcomas, have been treated with embolization.…”

Section: Discussionmentioning

confidence: 99%

Chemoembolization in Metastatic Liver Neoplasms: KADR Experience

Al-Ahwal

Rawas

Akbar

1999

med

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ABSTRACT. Objective: To assess the results of chemoembolization in this pilot study for patients with unresectable metastatic liver neoplasms.Methods: Patients with unresectable liver metastases secondary to different primary tumors who did not have decompesated liver disease underwent selective intra-arterial chemotherapy consisting of 5-flourouracil, adriamycin and cisplatin followed by embolization of the feeding artery using Poly Vinyl Alcohol Particles (PVAP). Courses of treatment were given every four to six weeks for a minimum of three courses.Results: Eight patients with bilateral multiple or diffuse liver metastasis underwent chemoembolization. Five of eight patients had good palliation of symptoms and improvement in their quality of life. Their average duration of palliation was 7.2 months. Median survival for all patients was seven months.Seven patients died within the first year from a diagnosis of liver metastasis. The last patient with carcinoid syndrome is still alive 36 months after diagnosis.Conclusion: Selective intra-arterial chemotherapy followed by embolization in this pilot study with unresectable liver metastases gives palliation of symptoms and improvement in the quality of life for almost half of our patients but for a short duration. Patients with neuroendocrine tumors may have longer duration of palliation and survival. Further randomized trials with a higher number of patients would be worthwhile pursuing.

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“…However, if local control fails, prognosis for both groups of patients is extremely poor, with median survival time being around 6 months (Woll et al, 1999;Chang et al, 1998;Balch et al, 2001). Melanoma is highly resistant to chemotherapy and immunotherapy and no systemic therapy has yet been shown to impact on survival of either patient group (Bedikian et al, 1995;Nathan et al, 1997;Tsao et al, 2004).…”

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confidence: 99%

Phase I trial combining gemcitabine and treosulfan in advanced cutaneous and uveal melanoma patients

et al. 2005

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Gemcitabine and treosulfan are DNA-damaging agents. Preclinical studies suggest that synergism exists when melanoma cells are exposed to both drugs concurrently. We conducted a phase I trial in advanced melanoma patients to determine the optimal dose of gemcitabine to be combined with treosulfan. Cohorts of three patients received increasing doses of gemcitabine, commencing at 0.5 g m À2 , followed by a fixed dose of 5.0 g m À2 treosulfan on day one of a 21-day cycle. Patients alternately received a first cycle of single-agent gemcitabine or treosulfan before subsequent cycles of both drugs. Peripheral blood lymphocytes were collected in cycles 1 and 2 at various time points until 48 h post-treatment. The single-cell gel electrophoresis (Comet) assay was used to measure chemotherapy-induced DNA damage. A total of 27 patients were enrolled, no objective responses were observed, but two uveal melanoma patients had minor responses. Dose-limiting myelosuppression was reached at 3.0 g m À2 gemcitabine. DNA single-strand breaks were detected 4 h post-gemcitabine, repaired by 24 h. DNA interstrand crosslinks were detected 4 h post-treosulfan, fully removed by 48 h. Following combination chemotherapy, treosulfan-induced DNA crosslinks persisted, still being detectable 48 h post-treatment, supporting the hypothesis that gemcitabine potentiates treosulfan-induced cytotoxicity. The recommended regimen for further study is 2.5 g m À2 gemcitabine combined with 5.0 g m À2 treosulfan.

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Treatment of uveal melanoma metastatic to the liver. A review of the M.D. Anderson Cancer Center experience and prognostic factors

Cited by 34 publications

References 0 publications

Combination chemotherapy for choroidal melanoma: ex vivo sensitivity to treosulfan with gemcitabine or Cytosine arabinoside

Combination chemotherapy for choroidal melanoma: ex vivo sensitivity to treosulfan with gemcitabine or Cytosine arabinoside

Chemoembolization in Metastatic Liver Neoplasms: KADR Experience

Phase I trial combining gemcitabine and treosulfan in advanced cutaneous and uveal melanoma patients

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