taxane and Skin-Neoplasms

Systemic agents are used in melanoma for adjuvant therapy and to treat metastatic disease. Currently, interferon-α is the only agent approved for adjuvant therapy. Six drugs are FDA approved for metastatic disease: dacarbazine, interleukin-2 (IL-2), vemurafenib, ipilimumab, dabrafenib, and trametinib. Vemurafenib and ipilimumab were approved in 2011, whereas dabrafenib and trametinib were approved in 2013.. This review will update the practicing dermatologist on the differences in efficacy, adverse events, and cost of systemic therapies available for the treatment of melanoma.. This article is a review of the current literature on systemic therapies for advanced melanoma. Key search words included "advanced melanoma," "systemic therapy," and "adjuvant therapy" with particular focus on the past 20 years.. Before 2011, dacarbazine and IL-2 were the only FDA approved therapies for metastatic melanoma, and IFN-α is the only approved agent for adjuvant therapy. The new agents vemurafenib, ipilimumab, dabrafenib, and trametinib are the first to have improved overall survival in Phase III studies in comparison with other systemic therapies.. Despite new developments, there remains a significant need for better therapies with improved long-term efficacy and decreased toxicity.

Topics: Animals; Antibodies, Monoclonal; Antineoplastic Agents; Bridged-Ring Compounds; Dacarbazine; Humans; Imidazoles; Indoles; Interferon-alpha; Interleukin-2; Ipilimumab; Melanoma; Oximes; Platinum Compounds; Protein Kinase Inhibitors; Pyridones; Pyrimidinones; Skin Neoplasms; Sulfonamides; Taxoids; Temozolomide; Vemurafenib

Angiosarcomas may be primary in the skin, primary in soft tissue or viscera, or secondary to irradiation. All angiosarcomas have a poor prognosis. Taxanes may have efficacy in the treatment of angiosarcoma. Expression of TLE3 has been associated with improved outcome in taxane-treated breast cancers. We studied a series of angiosarcoma with TLE3 immunohistochemistry. Cases of angiosarcoma (98 total cases; 37 cutaneous, 48 soft tissue/visceral and 13 post-irradiation) were retrieved and follow up was obtained. Tumors were classified as 'vasoformative', 'spindled', 'epithelioid' and 'mixed'. TLE3 immunohistochemistry was performed. Statistical analyses were performed. Patients (50 males and 48 females) had a median age of 60.2 years. Tumors had a median size 7.5 cm and were vasoformative (N = 43, 44%), spindled (N = 21, 21%), epithelioid (N = 16, 16%) and mixed (N = 18, 18%). Follow up was available for 89/98 patients (91%): 32 (36%) were dead due to disease, 36 (41%) were dead due to other causes and 21 (24%) remained alive. The median time to death was 2.1 years. TLE3 reactivity was observed in 0/37 (0%) cutaneous angiosarcomas, in 28/48 (58%) cases from soft tissue/viscera and in 4/13 (31%) post-irradiation angiosarcomas. (p = <0.0001). Improved 5-year survival was seen in vasoformative angiosarcomas (p = 0.03). TLE3 expression was not associated with taxane response. However, only a subset of patients was treated with taxane. Our study confirms the poor prognosis of angiosarcoma. Vasoformative angiosarcoma may have a more favorable prognosis. A lack of TLE3 expression in cutaneous angiosarcoma may reflect differing pathogenesis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Bridged-Ring Compounds; Child; Child, Preschool; Co-Repressor Proteins; Disease-Free Survival; Female; Hemangiosarcoma; Humans; Immunohistochemistry; Infant; Male; Middle Aged; Nuclear Proteins; Retrospective Studies; Skin Neoplasms; Survival Rate; Taxoids

This study was designed to evaluate the efficacy and safety of single-agent gemcitabine for the treatment of patients with anthracycline- and taxane-pretreated metastatic breast cancer (MBC). Eligible patients were required to have bidimensionally measurable MBC that had been treated with 2-4 prior chemotherapy regimens that included an anthracycline and a taxane. Gemcitabine was delivered at a dose of 800 mg/m2 on days 1, 8, and 15 of a 28-day cycle until evidence of disease progression.. Twenty-two patients were enrolled and included in the safety analysis; 18 patients were evaluable for response. The median age of patients was 54 years (range, 36-70 years). The mean number of prior chemotherapy regimens for metastatic disease was 2.3, and the mean dose of gemcitabine delivered was 911 mg/m2 (range, 600-1600 mg/m2).. Overall, gemcitabine was well tolerated with minimal grade 3 toxicities; the only grade 4 toxicity was 1 case of pulmonary embolus. Three patients had evidence of partial tumor regression (17%; 95% CI, 4%-41%), and 1 patient had a 41% decrease in tumor volume, including liver metastasis.. Gemcitabine is active and well tolerated as monotherapy given in heavily pretreated patients with MBC after anthracyclines and taxanes. The activity and safety reported in this trial are consistent with previous reports in similar patients.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Deoxycytidine; Dose-Response Relationship, Drug; Doxorubicin; Drug Administration Schedule; Female; Gemcitabine; Humans; Infusions, Intravenous; Liver Neoplasms; Lung Neoplasms; Middle Aged; Nausea; Neoadjuvant Therapy; Neoplasm Staging; Prognosis; Salvage Therapy; Skin Neoplasms; Soft Tissue Neoplasms; Survival Analysis; Taxoids; Treatment Outcome; Vomiting

Cutaneous angiosarcoma (CAS) is a rare and highly aggressive type of vascular tumor. Although chemoradiotherapy with taxanes is recognized as a first-line therapy for CAS, second-line therapy for CAS remains controversial. From the above findings, the efficacy and safety profiles of taxane-switch (change paclitaxel to docetaxel or vise), eribulin methylate, and pazopanib regimens in second-line chemotherapy were evaluated retrospectively in 50 Japanese taxane-resistant CAS patients. Although there was no significant difference in progression-free survival (P = 0.3528) among the regimens, the incidence of all adverse events (AEs) (P = 0.0386), as well as severe G3 or more AEs (P = 0.0477) was significantly higher in the eribulin methylate group and pazopanib group than in the taxane-switch group. The present data suggest that switching to another taxane should be considered for the treatment of taxane-resistant CAS in second-line therapy based on the safety profiles.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Neoplasm; East Asian People; Female; Hemangiosarcoma; Humans; Paclitaxel; Retrospective Studies; Skin Neoplasms; Taxoids

Cutaneous angiosarcoma (CAS) is a rare soft-tissue sarcoma of vascular endothelial origin. Paclitaxel (PTX) and docetaxel (DTX) are used as systemic chemotherapy; however, chemoresistance often occurs in CAS. Switching one taxane to the other (i.e., PTX to DTX, or vice versa) is an option when the first taxane is no longer effective in malignant cancers such as ovarian or breast cancer. However, the efficacy of the same strategy in CAS has not been reported. Herein, we report the clinical response of switching one taxane-based chemotherapy to the other in CAS patients with resistance to the first taxane. Twelve CAS patients were included for analyses. In all patients, the median overall survival from the start of the first taxane treatment was 29.0 months (range, 6.47-58.5). During the first taxane, the median PFS for all patients was 5.96 months (1.81-47.1). Similarly, the median (range) PFS for all patients during the second taxane was 5.87 months (1.60-18.2). Furthermore, the median OS was 22.7 months (PTX to DTX) and 39.5 months (DTX to PTX) (p = 0.307). The median PFS during the first taxane was 5.14 (PTX to DTX) and 12.5 months (DTX to PTX), respectively (p = 0.380). The median PFS during the second taxane was 3.5 (PTX to DTX) and 7.1 months (DTX to PTX), respectively (p = 0.906). The objective response rate, defined as the sum of complete response (CR) and partial response (PR) rates, was 16.7%. The disease control rate, defined as the sum of CR, PR, and stable disease rates, was 50%. The frequency of adverse events during the second taxane was the same between the two groups (p > 0.999). Our report suggests that CAS patients could benefit from the second taxane treatment if the tumor is resistant to the first taxane.

Topics: Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Hemangiosarcoma; Humans; Paclitaxel; Skin Neoplasms; Taxoids

Angiosarcoma is a rare malignant neoplasm derived from endothelial cells, and because advanced angiosarcoma is resistant to standard chemotherapy its prognosis is poor. Therefore, new therapies are urgently needed. Heat shock protein (HSP)90 has been identified as a molecular chaperone that regulates various cancer-related proteins. Numerous clinical trials are currently testing the effectiveness of HSP90 inhibitors in various types of malignancies.. To investigate the role of HSP90 in the pathogenesis of angiosarcoma and whether the inhibition of HSP90 may have antitumour activity.. The expression of HSP90 protein in angiosarcoma was examined using immunohistochemistry and immunoblotting. The effects of HSP90 inhibition were proven using proliferation, migration and invasion assay in angiosarcoma cells. The mechanism of antitumour effect by HSP90 inhibition was investigated by the transfection of small interfering RNA (siRNA).. The levels of HSP90 protein expression in cultured angiosarcoma cell lines were markedly increased compared with those in normal tissue cell lines. Immunohistochemical analyses revealed that the expression of HSP90 protein was strongly detected in angiosarcoma tissues compared with that in normal dermal vessels or senile angioma tissues. Ganetespib, an HSP90 inhibitor, with or without taxanes, inhibited the proliferation of angiosarcoma cells via apoptosis in a dose-dependent manner. HSP90 siRNA suppressed the proliferation, migration and invasion of angiosarcoma cells. Knock-down of HSP90 did not suppress vascular endothelial growth factor receptor 2 directly, but selectively suppressed several downstream targets of vascular endothelial growth factor signalling in angiosarcoma cells.. HSP90 could be a novel therapeutic target for angiosarcoma.

Topics: Anticarcinogenic Agents; Antineoplastic Agents; Bridged-Ring Compounds; Case-Control Studies; Cell Movement; Cell Transformation, Neoplastic; Hemangiosarcoma; HSP90 Heat-Shock Proteins; Humans; Signal Transduction; Skin Neoplasms; Taxoids; Triazoles; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A

Paclitaxel and docetaxel are antineoplastic drugs that bind the microtubules, producing the arrest of mitoses, which may be seen histopathologically. These histopathologic changes may simulate an intraepidermal keratinocytic malignant neoplasm, and an accurate diagnosis may be only established by clinicopathological correlation.. We report six cases of cutaneous eruptions by taxanes in which a striking cytotoxic effect was evident histopathologically.. Cutaneous biopsies were obtained in each patient.. Atypical starburst-like or ring-like mitoses and dyskeratosis on basal and suprabasal layers of the epidermis. Areas of squamous syringometaplasia were also seen in one case.. These findings were interpreted as expression of mitotic arrest due to taxanes. Similar changes have been described in association with other chemotherapeutic drugs such as vincristine, podophyllin and its derivative etoposide; colchicine, busulfan and maytansine, but cases like ours due to taxanes are exceptional or under-reported.. Dermatopathologists should be aware of these effects in order to interpret carefully cutaneous biopsy specimens of patients receiving taxanes.

Topics: Bridged-Ring Compounds; Diagnosis, Differential; Exanthema; Female; Humans; Male; Middle Aged; Skin; Skin Neoplasms; Taxoids

Although cutaneous angiosarcoma (cAS) has one of the worst prognoses among malignant skin tumors, few effective drug options for secondary treatment have been discovered to date because of the limited number of cases. Therefore, this study was aimed at determining pazopanib's potential as a new cAS treatment option. We retrospectively evaluated five patients with taxane-resistant unresectable cAS treated with pazopanib at a university hospital. Their characteristics and treatment outcomes were retrieved from their records. Progression-free survival (PFS), overall survival (OS), disease progression, and toxicity were evaluated; furthermore, the response to pazopanib was assessed in relation to the expression of vascular endothelial growth factor receptor 2 (VEGFR-2). The median PFS from the time of pazopanib initiation was 94 days. Two patients showed partial response, two showed stable disease, and one had progressive disease in the case of the best overall response. VEGFR-2 expression was positive in all cases, and patients with high expression had improved median OS compared to that in those with low expression. VEGFR-2 expression was correlated with a longer OS. The most common toxicities were hypertension and anorexia followed by myelosuppression. This is the largest case series reported wherein pazopanib was used for taxane-resistant cAS. Although the cytoreductive effect and survival benefits were not significant in this small sample, we consider pazopanib a valid treatment option for preserving patients' quality of life. Our results suggest pazopanib treatment slows the progression of disease and stabilizes it in patients with taxane-resistant cAS.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Bridged-Ring Compounds; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Hemangiosarcoma; Humans; Indazoles; Male; Middle Aged; Pyrimidines; Retrospective Studies; Skin Neoplasms; Sulfonamides; Taxoids

The prognosis of cutaneous angiosarcoma (CAS), especially for patients with tumours > 5 cm has been reported to be dismal, even after conventional surgery and radiotherapy (S + RT).. To demonstrate the efficacy of chemoradiotherapy with taxane (T + RT) and maintenance chemotherapy.. We retrospectively reviewed 16 patients with CAS treated with T + RT and 12 patients treated with S + RT. None had distant metastasis. Tumour sites included the scalp (n = 25) and limbs (n = 3). The chemotherapy regimens used in T + RT were monthly docetaxel (n = 10), biweekly docetaxel (n = 1), weekly docetaxel (n = 5) and weekly paclitaxel (n = 1). The median radiation dose was 70 Gy. Nine patients receiving T + RT continued chemotherapy as maintenance therapy (monthly docetaxel in nine patients and monthly paclitaxel in two patients) and four patients receiving S + RT received adjuvant chemotherapy (weekly docetaxel).. The response ratio of T + RT was 94% (14 complete remission and one partial remission). The 5-year overall survival (OS) rate of patients receiving T + RT was statistically higher than those receiving conventional S + RT (56% and 8%, respectively; P < 0·01). Moreover, patients who received T + RT with maintenance chemotherapy showed a significant improvement in OS than those receiving T + RT alone (P < 0·01). There was a strong trend for relapse-free survival, but it was not significant (P = 0·07). These data indicate that maintenance chemotherapy is crucial for long-term survival after T + RT.. From these results, we suggest that T + RT followed by maintenance chemotherapy is a plausible method for managing CAS, especially large tumours that are difficult to manage with S + RT alone.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Chemoradiotherapy; Combined Modality Therapy; Docetaxel; Drug Administration Schedule; Female; Head and Neck Neoplasms; Hemangiosarcoma; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Retrospective Studies; Scalp; Skin Neoplasms; Taxoids; Treatment Outcome

To show the efficacy of taxane-based chemotherapy for the treatment of cutaneous angiosarcoma.. A case-control study comparing patients who received taxanes without wide local excision (group A, n = 5) and patients who received conventional surgery-based therapy (group B, n = 8) in one university hospital in eastern Japan. Data were collected from a total of 13 patients with cutaneous angiosarcoma treated from November 1997 through July 2009.. Group A received taxanes: four patients received docetaxel, and one patient received paclitaxel. Radiation was used concomitantly in two patients. Marginal local excision was performed in two patients. Group B received wide local excision followed by radiation (six patients), docetaxel (three patients), and interleukin-2 (two patients). No patients in group A had local recurrence, whereas five out of the eight patients in group B did (p < 0.05, chi-square test). Median overall survival was 31 months in group A and 10 months in group B. Estimated overall survival using the Kaplan-Meier method was significantly longer in group A (p < 0.05, log-rank test).. In our series, taxane-based chemotherapy was superior to conventional surgery-based therapy. Our results indicated that taxane regimens without mutilating surgery offered both local control and prevention of metastasis, which led to prolonged survival.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Bridged-Ring Compounds; Case-Control Studies; Female; Hemangiosarcoma; Humans; Interleukin-2; Male; Middle Aged; Neoplasm Recurrence, Local; Radiotherapy, Adjuvant; Retrospective Studies; Skin Neoplasms; Taxoids

Metastatic breast cancer is a common clinical entity, and its treatment is still a major clinical problem in modern oncology. Both cisplatin (CDDP) and 5-fluorouracil (5-FU) are effective agents.. In this retrospective study, the therapeutic efficacy and tolerability of CDDP and continuous infusion of 5-FU were evaluated in patients with pretreated metastatic breast cancer. 16 patients were surveyed. All of them were pretreated with anthracyclines in an adjuvant and/or therapeutic setting. Eight of them also received taxanes after the failure of anthracyclines. CDDP at 80 mg/m(2) for 1 day and 5-FU at 1,000 mg/m(2) as a continuous 24-hour infusion for 5 consecutive days were administrated every 3 weeks.. 13 patients were included in response analysis. Because of severe toxicity, chemotherapy protocols of 3 patients were stopped after the first cycle. The objective response rate (partial response) was 46%. No complete response was observed. The median response duration was 5 (3.5-7) months in the response group. Favorable objective responses were observed more frequently in cases with skin metastasis. Five out of 6 patients who attained partial remission had skin metastasis. Response rates were similar in patients pretreated with taxanes and in those not pretreated with taxanes (75 vs. 80%). The most serious toxicity was myelosuppression (25%).. Although this study is based on only a limited number of patients, the combination of CDDP and 5-FU can be recommended in patients refractory to both anthracyclines and taxanes and especially in cases of skin metastasis with a good performance status.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intravenous; Middle Aged; Premedication; Skin Neoplasms; Taxoids; Treatment Outcome