Brain metastases of metastatic malignant melanoma: Response to DTIC and interferon-gamma

Summary The prognosis of patients with malignant melanoma and brain metastases is poor. Therapy of brain metastases is difficult and mostly unsuccessful, with brain metastases being the predominant factor which determines overall survival. We report here on a patient whose brain metastases responded to DTIC+INF-gamma. We present a short summary on the different effects on INF-alpha and INF-gamma and reach the conclusion that clinical trials which combine DTIC and INF-gamma should be performed. Based on this observation, combinations including INF-alpha are not necessarily comparable to modalities which include INF-gamma.     

腰部恶性血管外皮瘤1例附文献复习

目的：探讨恶性血管外皮瘤的诊断与治疗。方法：报道1例术后出现肝脏多发转移灶转移的腰部恶性血管外皮细胞瘤的诊断及治疗,并复习文献。结果：该患者于腰部恶性血管外皮瘤术后81月出现肝脏转移和局部复发,予环磷酰胺、阿霉素、顺铂化疗4疗程,化疗疗效评价为部分缓解。结论：部分恶性血管外皮瘤于术后5年后出现远处转移,其对化疗相对敏感,预后较好。     

腰部恶性血管外皮瘤1例附文献复习

目的:探讨恶性血管外皮瘤的诊断与治疗。方法:报道1例术后出现肝脏多发转移灶转移的腰部恶性血管外皮细胞瘤的诊断及治疗,并复习文献。结果:该患者于腰部恶性血管外皮瘤术后81月出现肝脏转移和局部复发,予环磷酰胺、阿霉素、顺铂化疗4疗程,化疗疗效评价为部分缓解。结论:部分恶性血管外皮瘤于术后5年后出现远处转移,其对化疗相对敏感,预后较好。     

Phase II study with the combination of gemcitabine and DTIC in patients with advanced soft tissue sarcomas

Purpose: Based on the promising results of a Phase I study with a combination of gemcitabine and DTIC performed in advanced soft tissue sarcoma (ASTS) patients, and due to the limited efficacy of second or third line therapies in those patients, we designed a Phase II study to determine the activity of this new regimen. Methods: Patients with ASTS, measurable disease, pretreated with chemotherapy, received gemcitabine 1,800 mg/m² infused over 180 min followed by DTIC 500 mg/m² (one cycle), every 2 weeks. The pharmacokinetics (PK) of gemcitabine and 2′,2′-difluorodeoxyuridine (dFdU), and the accumulation of gemcitabine triphosphate (dFdCTP) by peripheral blood mononuclear cells were studied. The influence of the sequence of administration on those parameters was examined to exclude potential drug interactions. Results: Twenty-six patients received a total of 158 cycles (mean four cycles, range 1–18). Grade 3–4 anemia (23% of patients), granulocytopenia (46%) or thrombocytopenia (12%), and grade 3 increase in AST (18%), ALT (21%), or γ-glutamyl-transferase (9%) were noted. Response rate in 23 patients was 4% (95% CI: 0–24%), and in 8 of 11 patients stable disease lasted > 6 months. Progression-free rate (PFR) at 3 and 6 months was, respectively, 48 and 28%, and median overall survival 37 weeks. Pooled data from the Phase I and Phase II studies showed clinical benefit in patients with leiomyosarcomas (LMS) (57%) and malignant fibrous histiocytomas (MFH) (33%). The sequence of administration did not influence PK of gemcitabine or dFdU. There was a trend (P = 0.11) toward a lower accumulation of dFdCTP when DTIC preceded gemcitabine. Conclusions: Although the remission rate was low, PFR figures indicate that this regimen has activity in patients with ASTS. It should be compared with DTIC, or other gemcitabine-containing combinations, in patients with LMS or MFH, to determine whether this combination offers advantages in PFR or in overall activity.J. Fra and R. Losa contributed equally to this work.     

61例恶性胸腺瘤患者治疗分析

目的：探讨恶性胸腺瘤的治疗方法及其疗效。方法：回顾分析61例恶性胸腺瘤的临床资料。按治疗方法分为完全切除组32例，部分切除组26例和探查组3例，每组中均有放疗和非放疗患者。以术后5年复发率和生存率做为疗效指标进行分析。结果：术后放疗患者5年复发率低于同组未放疗患者，5年存活率高于未放疗患者，大部切除结合放疗组与完全切除结合放疗组的5年复发率（P=0．926），生存率（88．9％VS86．4％）之间无显著差异。结论：胸腺恶性肿瘤因浸润性生长，多不能完全切除，术后结合放疗有助于控制局部复发和提高存活率。     

A combination chemotherapy of ACNU and DTIC for advanced malignant melanoma

Fourteen patients with advanced malignant melanoma were treated with a combination chemotherapy consisting of ACNU 100 mg/m2 i.v. on Day 1 in 6 week intervals and DTIC 200 mg/m2 i.v. on Days 1 to 5 at 3 week intervals. Four patients had prior chemotherapy and 2 had prior immunotherapy. Excluding 4 patients received the regimen for adjuvant chemotherapy, 10 of 14 patients were evaluable for response. There were 3 patients of partial responses, 3 minor responses, 1 no change, and 3 progressive diseases. The durations of partial responses were 1, 1, and 8 months, respectively, while the survival times in these patients were 5, 21, and 10 months, respectively. Leukopenia less than 4,000/cmm occurred in 10 of 14 patients (71%) and thrombocytopenia less than 100 X 10(3)/cmm in 9 of 14 patients (64%), moreover, these hematologic toxicities were cumulative. Serum GOT and GPT elevated to 3,460 mu/ml and 1,365 mu/ml, respectively in one patient, but this returned to a normal level one month later. Nausea and vomiting were mild to severe in 12 of 14 patients, being most marked on Day 1 and decreasing intensity during the next several days. Other non-hematologic toxicities including skin rash, fever, and phlebitis were noted in each one patient, respectively. Hematologic toxicity of this regimen was a dose limiting toxicity; therefore, intensive supportive therapy to prevent infection and hemorrhage is essential for the management of the patients during this chemotherapy.     

Treatment of esthesioneuroblastoma with chemotherapy: A report of two cases

Esthesioneuroblastoma is an uncommon tumor arising from the olfactory epithelium within the nasopharynx. Conventional treatment consists of surgical resection and irradiation. The use of chemotherapy in limited responses has been reported using cyclophosphamide, thio-TEPA, nitrogen mustard, vincristine, doxorubicin, and chlorambucil as single drugs or in various combinations. Two cases are presented in which neurologic involvement prompted the application of intraventricular methotrexate by an implantable constant infusion drug delivery system in one patient and intra-arterial cis-platinum in combination with intravenous 5-fluorocytosine in a second patient. The tumor of the first patient responded to irradiation followed by methotrexate for four years. The second patient experienced a brief response to the combined chemotherapy following surgery for a recurrent esthesioneuroblastoma. A brief review of the literature regarding chemotherapy and the aggressive form of esthesioneuroblastoma is presented.     

Experience with interferon alpha 2b combined with dacarbazine in the treatment of metastatic malignant melanoma

A prospectively randomized trial was undertaken to compare dacarbazine (DTIC) alone with DTIC plus interferon in patients with metastatic malignant melanoma. Of the 73 patients who entered on the study, 36 were randomized to receive DTIC alone and 37 were randomized to receive the combination DTIC plus interferon. The two sections were well balanced. There was more toxicity on the combination section, but no life threatening toxicity. The overall response rate for patients on DTIC was 20% (two complete and five partial responses)(95% CI 7–39%) and for patients on DTIC plus interferon was 50% (13 complete and four partial responses)(95% CI 26–72%) (p=0.007). The median time to treatment failure, was significantly more in favour of the combination treatment (9versus 2.5 months;p < 0.01, Mantel-Cox). The median survival of 16.7versus 8 months was in favor of the combination treatment (p < 0.01). The reasons for the improved results with the combination treatment are discussed. The Eastern Cooperative Oncology Group is currently, based on the results of this study, investigating the role of interferon combinations in metastatic malignant melanoma     

Delayed pulmonary metastasis and recurrence of intracranial malignant solitary fibrous tumor/hemangiopericytoma: Case report and literature review

Solitary fibrous tumors/hemangiopericytomas (SFTs/HPCs) are intracranial spindle cell tumors that originate from interstitial tissue. SFTs/HPCs that are primary malignant intracranial tumors are exceedingly uncommon. A case of intracranial malignant SFT/HPC that originated intracranially and spread to the pulmonary region is described herein. Furthermore, the specimens from two surgical resections obtained when the patient had undergone two prior procedures for intracranial ‘meningiomas’ were also reviewed. The results of the lung biopsy matched the morphologic appearance of the intracranial tumor. The patient died ~2 years after the chest pain started. In addition, the literature was reviewed. According to previous studies, STAT6 expression was positive in 100% of SFTs/HPCs and radiologic characteristics assisted in determining the tumor pathology and grade. Surgical management has been the mainstay treatment for SFTs. In cases of incomplete resection, adjuvant radiotherapy is effective and rigorous follow-up is required to monitor for recurrence.     

Chemotherapy of metastatic soft tissue sarcoma with a combination of adriamycin and DTIC or adriamycin and ifosfamide

Between 1982 and 1986, 38 patients with soft tissue sarcomas were treated with a combination of ADM/DTIC (group A), another 45 (group B) received ADM/IFO between 1986 and 1990. Clinical characteristics were comparable in both groups. Remission rate was 34% in group A and 43% in group B. Duration of remission was 10 months and median survival 13 months in both groups. Toxicity, especially myelotoxicity, was severe without marked differences between both groups. We conclude that adriamycin/DTIC and adriamycin/ifosfamide are both active regimens in metastatic soft tissue sarcomas, nevertheless, overall prognosis remains poor.     

Merkel细胞癌治疗方法探讨

目的　探讨Merkel细胞癌的规律及其治疗方法。方法　通过对 4例的治疗体会和国内外文献的复习 ,进行总结分析。结果　 4例中 2例发生局部复发 ,3例出现区域淋巴结转移 ,2例出现远地转移 ,1例死亡 ,与文献报道的结果相似。结论　Merkel细胞癌有明显的局部复发及早期转移倾向。Ⅰ期病例强调术后放射治疗 ,Ⅱ期病例应术后放射治疗加化疗 ,Ⅲ期病例做化疗和放射治疗的综合治疗。     

Acute leukaemia following malignant ependymoma: a case report

Though an increasing number of chemotherapy- and radiotherapy-related leukaemias are being reported, acute promyelocytic leukaemia developing as a therapy-related second malignancy is still uncommon. Here we report a case of acute promyelocytic leukemia, microgranular variant, developing in a case of intracranial malignant ependymoma, 1.5 years following treatment with craniospinal radiotherapy.     

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

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.     

高剂量表柔比星为主的联合化疗方案治疗48例晚期胸部恶性肿瘤

目的：评价高剂量表柔比星（表阿霉素）联合其他化疗药物治疗晚期胸部肿瘤的疗效及毒副反应。方法：48例可评价晚期胸部肿瘤中非小细胞癌32例;乳腺癌11例;纵隔恶性淋巴瘤5例。分别应用EMP[表柔比星（EPI）100mg/m^2联合丝裂霉素（MMC)6mg/m^2及顺铂（DDP）60mg/m^2]治疗非小细胞肺癌;应用CEF[环磷酰胺（CTX）600mg/m^2联合表柔比星100mg/m^2及氟尿嘧啶（5－FU）800mg/m^2]治疗乳腺癌。应用CEOP[环磷酰胺600mg/m^2联合表柔比星100mg/m^2、长春新碱（VCR）1mg/m^2及强的松60mg/m^2]治疗纵隔恶性淋巴瘤。3－4周重复。结果：非小细胞肺癌总有效率56．3％;乳腺癌总有效率72．7％;纵隔恶性淋巴瘤总有效率100％。白细胞减少为主要毒副反应,发生率为93．8％。未见明显心脏毒性。结论：高剂量表柔比星治疗晚期胸部恶性肿瘤安全有效。     

Kinetically directed combination therapy with adriamycin and X-irradiation in a mammary tumor model

In the present studies, the interaction of adriamycin (A) and x-irradiation (X) in T1699 mouse mammary tumors was evaluated. Mitotic indices and thymidine labeling indices were determined at various intervals after A or X alone, and after A + X given in combination. The results with A (1.0 mg/kg) and X (200 R) alone suggests that those quantities of each agent induce a G₂ progression delay of 9–12 brs. The kinetic results after A + X in combination indicated increased S phase transit. time and G₂ progression delay. Recovery kinetics after A + X were used to predict “optimmn” sequence intervals for subsequent A + X fractions. Sequential A + X treatment schedules, up to 4 fractions, were designed and evaluated by regrowth delay measurements. The results indicated that the interaction was additive when A and X were given together in combination. Fractionation of A + X to minimize proliferstive recovery between fractions resulted in an enhanced antitumor effect.     

眼眶血管外皮细胞瘤：20例临床病理分析及超微结构观察

眼眶血管外皮瘤２０例，其病理特点为Ｌ丰富的血管网，血管之间大量增生的梭形细胞，单个瘤细胞外有网状纤维包绕。根据肿瘤的异形程度及核分裂的数量诊断为良性，低度恶性及恶性血管外皮瘤．１０刚以下患诊诊断性要慎重。     

Management of Cerebral Metastases from Malignant Melanoma: Results of a Combined,Simultaneous Treatment with Fotemustine and Irradiation

We report results of a conservative treatment for brain metastases from malignant melanoma with a combination of irradiation and chemotherapy (fotemustine and/or DTIC). To date, 12 patients have been treated. There was a complete remission of the brain metastases in four patients. In two patients a partial remission was observed. The mean survival of the responder was 8.2 months (95% confidence interval 3.8–12.6 months). The most common side effects were thrombocytopenia, leukopenia, and alopecia. Altogether, the treatment was well tolerated. As the outcome of patients with brain metastases from malignant melanoma is generally poor, this combined chemo- and radiation therapy may provide improved care for such patients.     

Activity of temozolomide and bevacizumab in the treatment of locally advanced, recurrent, and metastatic hemangiopericytoma and malignant solitary fibrous tumor

BACKGROUND:

Hemangiopericytomas and malignant solitary fibrous tumors (HPC/SFT) are rare, closely related sarcomas with unpredictable behavior that respond infrequently to chemotherapy. An optimal systemic treatment strategy for advanced HPC/SFT has not yet been identified.

METHODS:

We retrospectively analyzed the records of 14 patients with histopathologically confirmed HPC/SFT who were treated at The University of Texas MD Anderson Cancer Center between May 2005 and June 2007. All patients were treated with temozolomide 150 mg/m² orally on days 1‐7 and days 15‐21 and bevacizumab 5 mg/kg intravenously on days 8 and 22, repeated at 28‐day intervals. Computed tomography assessment of tumor size and density (Choi criteria) was used to determine the best response to therapy. The Kaplan–Meier method was used to estimate progression‐free survival.

RESULTS:

The median follow‐up period was 34 months. Eleven patients (79%) achieved a Choi partial response, with a median time to response of 2.5 months. Two patients (14%) had stable disease as the best response, and 1 patient (7%) had Choi progressive disease as the best response. The estimated median progression‐free survival was 9.7 months, with a 6‐month progression‐free rate of 78.6%. The most frequently observed toxic effect was myelosuppression.

CONCLUSION:

Combination therapy with temozolomide and bevacizumab is a generally well‐tolerated and clinically beneficial regimen for HPC/SFT patients. Additional investigation in a controlled, prospective trial is warranted. Cancer 2011;. © 2011 American Cancer Society.     

头颈部恶性黑色素瘤28例的治疗及预后因素

目的：探讨影响恶性黑色素瘤的治疗及其预后因素。方法：本院头颈外科1984年-1994年10年间诊断28例恶性黑色素瘤,治疗方法分广泛切除,广泛切除加预防性颈清扫术,广泛切除加治疗性颈清扫术3组,并作回顾性分析。结果：28例患者外院局部切除23例,残留率34.8%。原发灶切除范围分≤2cm组及＞2cm组,五年生存率分别为58%及40%。上述3组的五年生存率分别为80%、80%及39%。结论：原发灶的处理要规范,切除范围2cm以内。对颈淋巴结未及肿大的患者可暂不行颈淋巴结清扫术。颈洒巴结阳性患者可依原发灶的部位不同施行不同方式的颈清扫术,并强调颈清扫术中皮片分离应在颈阔肌浅面进行,以减少术后复发。     

放射治疗诱发恶性肿瘤8例临床分析及文献复习

目的：研究肿瘤放射治疗后诱发恶性肿瘤发生的因素。方法：回顾性分析15年中放射诱发的8例恶性肿瘤,其中原发肿瘤是宫颈癌的5例、上颌窦癌的1例,霍奇金淋巴瘤（HD）1例,子宫内膜癌1例。放射源为6MV—X射线及^192Ir源,常规分割照射,照射剂量为46—70Gy。结果：8例放射治疗后3．6—11年在原照射部位出现了肿瘤,其中5例宫颈癌诱发了直肠腺癌3例、膀胱移行细胞癌1例、子宫内膜腺癌1例;1例上颌窦鳞癌诱发了上颌骨骨肉瘤;1例HD诱发了白血病;1例子宫内膜癌诱发右腹股沟横纹肌肉瘤。结论：放射治疗可以诱发恶性肿瘤,主要与照射剂量、照射时年龄、照射部位及照射体积有关。