Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of malignant melanoma has increased at an alarming rate over the past few decades. Indications are that it will continue to rise in the foreseeable future. Primary prevention of malignant melanoma through education of the general public regarding the hazards of sun exposure is important in an attempt to reduce the incidence of the disease in the future. It can, however, be expected to take many years before a decrease in the number of cases of this disease is seen. Until such time, the medical oncologist will be faced with an increasing number of referrals for both adjuvant therapy and treatment of metastatic disease. Many agents have been investigated as possible postsurgical adjuvant therapies in patients with malignant melanoma. To date, inteferon-alpha (IFN-alpha) given initially intravenously in high doses followed by subcutaneous therapy for 1 year, is the only treatment that has been shown to increase disease-free and overall survival in patients with high-risk melanomas. Patients falling into this group should still, wherever possible, be enrolled in prospectively randomised clinical trials. Although the prognosis for patients with metastatic melanoma remains poor, some progress in the management of this disease has been made. It has not yet been conclusively proven that combination chemotherapy yields superior results to single agent dacarbazine (DTIC) [which has for many years formed the cornerstone of therapy]. Immunotherapy involving IFNs and interleukin-2 (IL-2) alone or in combination has yielded similar results to those achieved with chemotherapy alone. The combination of chemotherapy plus immunotherapy appears to hold promise, with high response rates and often durable remissions reported, albeit at the expense of considerable treatment-related toxicity. Novel therapies including tumour vaccines and gene therapy also hold promise for the future management of this disease.
 ...
PMID:Current treatment options for malignant melanoma. 961 94

Inspired by the high response rates achieved with the DBCT regimen (dacarbazine [DTIC], carmustine [BCNU], cisplatin and tamoxifen [TAM]), we administered the nitrosourea compound fotemustine, cisplatin and TAM (FCT regimen) to 69 patients with metastatic melanoma. Fotemustine (100 mg/m2) and cisplatin (100 mg/m2) were administered every 4 weeks, preceded by TAM 160 mg daily for 7 days from the second course onwards. Pharmacokinetic blood sampling was performed in 14 patients during the initial two cycles to compare the pharmacokinetic behaviour of fotemustine with or without TAM. Previous chemo- or radiotherapy was allowed, and patients with brain metastases or concomitant other malignancies were included. Four complete and 11 partial responders were observed among 66 evaluable patients, yielding a response rate of 22.7% (95% confidence interval 12.9 32.5%). The median survival time was 6.4 months (range 0.1-52+ months). The main toxicities were thrombocytopenia, protracted nausea/vomiting and ototoxicity. Renal toxicity was generally mild, but possibly contributed to two deaths. Seven patients experienced deep venous thrombosis during the study. TAM had no influence on the pharmacokinetics of fotemustine. The activity of the FCT regimen was clearly inferior to that initially reported with DBCT treatment. However, a recent publication concludes that the latter achieves a considerably lower response rate when administered to a larger patient group. We believe our results reflect the true activity of FCT and similar regimens when administered routinely to unselected patients. Considering the number of potentially serious side effects, we cannot recommend the moderately active FCT regimen as a palliative treatment option for melanoma patients.
 ...
PMID:Clinical experience of fotemustine, cisplatin and high dose tamoxifen in patients with metastatic malignant melanoma. 991 19

The therapeutic benefit of adding interferon alpha (IFNalpha) to established single-agent and combination chemotherapy regimens for the treatment of metastatic melanoma has not been proven. We designed the present study to estimate the response rate of IFNalpha, dacarbazine, cisplatin and tamoxifen in patients who had not been treated with systemic therapy for advanced disease. Using a schedule similar to that which had previously been shown to favor IFNalpha plus dacarbazine over dacarbazine alone, we treated patients with an "induction" regimen of IFNalpha, 15 mU m(-2) day(-1) intravenously 5 days/week for 3 weeks. Following induction, schedules of IFNalpha, 5 mU m(-2) day(-1) subcutaneously three times a week, and tamoxifen, 10 mg orally twice a day, were begun. Dacarbazine, 250 mg m(-2) day(-1) and cisplatin 33 mg m(-2) day(-1) for 3 consecutive days were repeated every 4 weeks, and subcutaneous IFNalpha and oral tamoxifen were continued until the discontinuation of chemotherapy. We treated 25 patients (18 men and 7 women, median age 52 years) and observed only 1 objective response (response rate 4%, 95% confidence interval 0.1%-20%). The toxicities of the regimen consisted of moderate myelosuppression and constitutional side-effects. On the basis of the low antitumor activity of this regimen, we do not recommend it for further study or for use as standard therapy of metastatic melanoma.
 ...
PMID:Phase II trial of biochemotherapy with interferon alpha, dacarbazine, cisplatin and tamoxifen in metastatic melanoma: a Southwest Oncology Group trial. 1035 34

Therapy of metastatic melanoma still remains difficult. All therapeutic strategies have to consider the individual patient's condition and number and localisation of the metastases. Solitary metastases in lung, CNS, soft tissues and lymph nodes have to be removed by surgery. Multiple metastases are treated with a systemic chemoimmunotherpy. Promising approaches use interleukin-2, interferons, DTIC, temozolamide, vindesine and cisplatin. Radiotherapy is the treatment of first choice for bone and CNS metastases. These therapeutic strategies have improved the prognosis of metastatic melanoma. Additional multi-center trials and experimental approaches will help to reach the goal of a curative systemic therapy for metastatic melanoma.
 ...
PMID:[Systemic therapy of metastatic melanoma]. 1042 Aug 16

Melanoma is an uncommon disease in Japan. The incidence, however, has been gradually increasing in the last two decades, as in many other countries worldwide. Ten patients with metastatic malignant melanoma were treated between March of 1997 and April of 1998 in the Department of Dermatology, National Cancer Center Hospital, with a combination chemotherapy consisting of dacarbazine (DTIC), nimustine hydrochloride (ACNU), cisplatin (CDDP), and tamoxifen (TAM). The patients characteristics were as follows: four were males and six females; the age range was 33-70 years; all were Japanese; sites of primary disease: extremities 4, primary unknown 3, nasal cavity 1, anus 1, scalp 1; sites of metastases: lymph nodes 6, pulmonary system 5, skin 2, liver 3, gall bladder 1, adrenal gland 1. The chemotherapy regimen included DTIC 220 mg/m2/i.v. on days 1 through 3, ACNU 60 mg/m2/i.v. on day 1, cisplatin 25 mg/m2/i.v. on days 1 through 3, and tamoxifen 10 mg p.o. twice daily. One patient achieved a complete response and 3 showed partial responses. The response rate was 40%. The four responders included those with metastases to the nodes, lung, and liver. The main toxicities were nausea, vomiting, leucopenia, anemia, and thrombocytopenia. This regimen is a fairly effective combination against metastatic melanoma.
 ...
PMID:Dacarbazine, nimustine hydrochloride, cisplatin and tamoxifen combination chemotherapy for advanced malignant melanoma. 1048 2

The aim of this study was to evaluate the toxicity and efficacy of a monochemotherapy regimen of dacarbazine (DTIC), tamoxifen , interferon-alpha2a and interleukin-2 (IL-2) and two polychemotherapy regimens of cisplatin, DTIC, vindesine, tamoxifen, interferon-alpha2a with or without IL-2 in patients with metastatic melanoma. Consecutive patients with metastatic melanoma were enrolled in this trial and were randomized to arm A, consisting of DTIC 800 mg/m2 every 21 days, IL-2 9 MIU subcutaneously days 1-5 and 8-12, arm B, consisting of cisplatin 30 mg/m2 days 1-3, DTIC 250 mg/m2 days 1-3 and vindesine 2.5 mg/m2 day 1 every 28 days (CVD), or arm C, consisting of CVD plus IL-2 6 MIU days 1-5 and 8-12 every 28 days. In all three arms Interferon 3 MU subcutaneously three times a week and tamoxifen 20 mg orally were given throughout. Ninety-two patients were included in this study. Patient characteristics in the three groups were well balanced. The three regimens were delivered on an outpatient basis without major toxicity. The toxicities that did occur consisted primarily of flu-like symptoms in the IL-2 arms (A and C) and haematological toxicities in the CVD arms (B and C). No grade IV toxicities were encountered and no treatment-related deaths occurred. The total response rate was 13% in arm A, 35% in arm B and 37% in arm C. The median duration of response was 6 months and the median survival was 11 months. According to this phase II randomized trial polychemoimmunotherapy with CVD has an objective response rate of 35-36%, while monochemoimmunotherapy with DTIC has a response rate of 13%.
 ...
PMID:Multi-institutional phase II randomized trial of integrated therapy with cisplatin, dacarbazine, vindesine, subcutaneous interleukin-2, interferon alpha2a and tamoxifen in metastatic melanoma. BREMIM (Biological Response Modifiers in Melanoma). 1059 17

This study assessed response rates to combination dacarbazine (DTIC), BCNU (carmustine), cisplatin and tamoxifen (DBPT) chemotherapy in patients with progressive metastatic melanoma previously treated with DTIC, as an evaluation of DBPT as a second-line regimen, and as an indirect comparison of DBPT with DTIC. Thirty-five consecutive patients received DBPT. The patients were divided into two groups. Group 1 comprised 17 patients with progressive disease (PD) on DTIC + tamoxifen therapy who were switched directly to DBPT. Group 2 comprised 18 patients not immediately switched to DBPT and included patients who had either a partial response (PR; one patient) or developed stable disease (SD; four patients) with DTIC, or received adjuvant DTIC (nine patients). All except four patients had received tamoxifen at the time of initial DTIC treatment. Median times since stopping DTIC were 22 days (range 20-41) and 285 days (range 50-1,240) in Groups 1 and 2 respectively. In Group 1, one patient developed SD for 5 months and the remainder had PD. In Group 2, there were two PRs, four patients with SD (4, 5, 6, and 6 months), and 11 with PD. These results indicate that the DBPT regimen is not of value in melanoma primarily refractory to DTIC. There were responses in patients not directly switched from DTIC to DBPT, suggesting combination therapy may be of value in a small subgroup of melanoma patients.
 ...
PMID:Phase II study of second-line therapy with DTIC, BCNU, cisplatin and tamoxifen (Dartmouth regimen) chemotherapy in patients with malignant melanoma previously treated with dacarbazine. 1083 87

Dacarbazine (DTIC) is the only single-agent approved by the Food and Drug Administration for treating metastatic melanoma. With DTIC as single agent, an approximately 20% objective response rate can be achieved with median response duration of 5 to 6 months and complete response rates of 5%. Current status of DTIC single agent and DTIC-based combination chemotherapy has been extensively reviewed in this article. Moreover, future directions including new combination chemotherapies and/or new therapeutical approaches have been considered. The addition to DTIC of agents such as cisplatin, nitrosoureas and tubular toxins has been reported to yield high response rates, up to 40%, in single-institution phase II trials. Historically, promising combination regimens like BOLD (bleomycin, vincristine, lomustine and DTIC) and CVD (cisplatin, vinblastine and DTIC) have induced responses on metastatic lesions to the liver, bone and brain, commonly unresponsive to DTIC alone, even though have failed to produce impact on patient survival. Several other studies have suggested a significant enhancement of antitumor effect associated with the addition of tamoxifen to various cytotoxic regimens. The four-drug combination CBDT (cisplatin, carmustine, DTIC and tamoxifen) or "Dartmouth regimen" has yielded high response rates, up to 55%, with continuous, maintained, complete responses, up to 82 months, in a subset of patients, that is considerably longer than observed with other combinations. Some authors recommend CBDT as reference therapy, even though recently presented results of a randomized phase III trial of CBDT versus DTIC alone, show no statistical difference in survival between the two groups. While a survival benefit from DTIC-based chemotherapy or DTIC alone has never been shown in metastatic melanoma patients and, therefore, the survival has remained unchanged over the past 30 years, some long term survivors have been reported with the "Dartmouth regimen" and/or with high dose interleukin-2 (IL-2) based regimens whose role is going to be defined in prospective randomized phase III trials. On the other hand, the better understanding of the mechanisms responsible for melanoma chemoresistance and the development of new therapeutical strategies could change the scenario in the next future.
 ...
PMID:Dacarbazine-based chemotherapy for metastatic melanoma: thirty-year experience overview. 1084 Sep 32

We present the results of our chemo-biotherapy protocol for patients with metastatic melanoma. The rationale for the design of the combined therapy was induction of systemic anti-tumor immunity by: (a) priming with IFN-alpha for enhancement of tumor and histocompatibility antigen expression, (b) therapy by the 4-drug regimen (BCNU, DTIC, cisplatin and tamoxifen) for maximal tumor destruction, followed by (c) an immunomodulatory, low dose of GM-CSF. Treatment was given in cycles of three weeks: first IFN-alpha (3 x 10(6) U/day on days 1, 3, and 5); then the 4-drug regimen given according to Del Prete et al., (4); followed by GM-CSF (20 micrograms/m2/day on days 15 to 21). All patients were previously untreated by chemotherapy, and had a performance status of ECOG 0-2. Treatment was discontinued upon severe toxicity or disease progression. In responding patients--once maximal response was achieved-IFN alpha treatment (3 x 10(6) U/day, three times weekly) was continued for a period of two years or until disease progression. All 40 patients (28 males and 12 females) who received the above program were evaluable for response and toxicity and received at least two cycles of therapy. At a median follow-up of one year, 50% had achieved an objective response, with 22.5% complete responses (CR), and 27.5% partial remissions (PR). Median duration of response is 11 months (12 for CR and 9 for PR patients). Median survival for all patients is 14 months (range, 7-21), increasing to 22 months (range, 15-29) in responding patients. Activation of patients' peripheral blood Macrophages and Dendritic Cells was observed following GM-CSF treatment. The chemo-biotherapy protocol presented above--while associated with acceptable toxicity--resulted in a relatively high response rate with an increase in the number of durable responses in patients with metastatic melanoma.
 ...
PMID:A sequential four-drug chemotherapy and biotherapy with interferon alpha and GM-CSF--an innovative protocol for the treatment of metastatic melanoma. 1085 Mar 51

The main use of systemic chemotherapy in metastatic melanoma remains palliative. Dacarbazine (dimethyl-1-triazeno imidazole-4-carboxamide [DTIC]) is the standard chemotherapy agent for advanced disease. The combination chemotherapy and biochemotherapy regimens have achieved higher response rates, but have not led to durable remission or improved survival. The field of systemic therapy remains in need of a more effective and less toxic treatment strategy.
 ...
PMID:Systemic chemotherapy. 1094 65


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>