Evaluation of merbarone (NSC 336628) in disseminated malignant melanoma

Merbarone, NSC 336628, is an investigational anticancer drug with activity against experimental animal tumors including melanoma. This paper presents results of a Phase II clinical study of merbarone in patients with biopsy proven stage IV malignant melanoma without prior chemotherapy and with no evidence of CNS involvement. Thirty-five patients with median age 58 (range 27–81), with performance status 0–2 were treated with merbarone 1000 mg/m²/day for five days by intravenous continuous infusion repeated every 3 weeks. All patients (21 males and 14 females) were evaluable for toxicity. Two patients were not evaluable for response having been removed from protocol treatment due to toxicity and received other treatment during the first course of chemotherapy. Among the evaluable patients there was one complete response in a supraclavicular lymph node lasting four months and one partial liver response lasting three months. The remaining thirty-one patients were non-reponders. Of these one had a stable disease lasting 21 months. The overall objective response rate was 6% (2/35) with a 95% confidence interval of 1%–19%. Twenty-six of the 35 patients have died. The estimated median survival of the entire group was 9 months with a 95% confidence interval of six to eleven months. Renal toxicity was dose-limiting and manifested as increasing serum creatinine (54% of patients), proteinuria (51%) and hematuria (9%). One patient experienced grade 4 creatinine increase, proteinuria and acute renal failure. Other toxicities included nausea (71%), vomiting (51%), malaise (23%), weakness (20%), alopecia (17%), diarrhea (17%), anorexia (14%), transaminase (SGOT, SGPT) increase (14%), constipation (14%), alkaline phosphatase or 5nucleotidase increase (9%), and fever (9%). Hematologictoxicity (granulocytopenia, leukopenia, and anemia) was generally mild and infrequent (29%, only one patient had grade 4 granulocytopenia). Overall 9 patients (26%) had at least one grade 3 toxicity. We conclude that merbarone at this dose and schedule has detectable but minimal activity in the treatment of metastatic malignant melanoma and given the significant renal toxicity this schedule does not merit further evaluation in this disease.     

Phase II trial of docetaxel in patients with recurrent malignant glioma: a study of the National Cancer Institute of Canada Clinical Trials Group

Summary Background. We conducted a phase II study to determine the response to, and toxicity of, docetaxel (Taxotere; Rhône Poulenc Rorer Pharmaceuticals, Inc) in patients with recurrent malignant glioma. Patients and methods. Eighteen patients with recurrent malignant glioma were treated with 100 mg/m² (no prior chemotherapy) or 75 mg/m² (prior adjuvant chemotherapy) of docetaxel intravenously over 1 hour, every 3 weeks. Premedication with dexamethasone, diphenhydramine and ranitidine or cimetidine was given to all patients. Five (28%) had gioblastoma multiforme (GBM) and the rest other malignant gliomas. Eleven (61%) had an ECOG performance status of 0 or 1, and 13 (72%) were on corticosteroids at the start of treatment. Rigorous response criteria were used. All were eligible and évaluable for response. Results. No complete or partial responses were observed; the objective response rate was 0% (95% confidence interval: 0–15.3%). Patients received a median of 2 cycles (range, 1–6). Grade 3 or 4 neutropenia occurred in 17 (94%) patients and was associated with fever that required intravenous antibiotics in 4 (22%) patients. An additional patient received intravenous antibiotics for an infection not associated with neutropenia. Six (33%) patients had mild hypersensitivity reactions. Onychodystrophy, peripheral edema and peripheral neuropathy were uncommon and mild. Conclusions. Docetaxel has no significant activity in patients with recurrent malignant glioma.     

Phase II study of elsamitrucin (BMY-28090) for the treatment of patients with refractory/relapsed non-Hodgkin's lymphoma

Summary Purpose: To determine the response rate of patients withrefractory/relapsed non-Hodgkin's lymphoma to treatment with elsamitrucin and to further characterize the toxic effects of elsamitrucin in this group of patients. Patients and methods: Eligibility required pathologically verified relapsed or refractory non-Hodgkin's lymphoma with no more than two prior chemotherapy regimens for patients with tumors classified by the International Working Formulation (IWF) as A-C and no more than one prior chemotherapy for those with IWF grades D-G. Patients were entered with either normal or impaired bone marrow function, but normal liver function tests were required unless clearly related to lymphomatous involvement of the liver. Elsamitrucin 25 mg/m² was administered intravenously over 5–10 minutes weekly. Results: Thirty-one patients entered the study and were treated for a median of six weeks (range 1–42). All patients were évaluable for toxicity and 30 for response. Mild nausea and/or vomiting and asthenia were the most frequently reported adverse events. Four (13%, 95% CI 4.4–31.6%) partial responses were seen along with two (7%) minor responses while 9 (30%) patients had stable disease. Conclusion: Elsamitrucin showed modest activity in patients with relapsed or refractory non-Hodgkin's lymphoma. Toxicity was relatively mild, consisted mainly of asthenia, nausea and vomiting and did not include myelosuppression. The activity of elsamitrucin in this group of patients and its lack of myelosuppression suggest utility in this disease especially when combined with other proven agents.Presented in part at the 8th NCI-EORTC Symposium on New Drugs in Cancer Therapy, Amsterdam, The Netherlands, March 1994.     

Phase II evaluation of topotecan in patients with advanced colorectal cancer. A Southwest Oncology Group trial (SWOG 9241)

The topoisomerase-1 inhibitor, topotecan, was tested in 48 eligible patients with advanced colorectal cancer. The patients had no prior chemotherapy and a Southwest Oncology Group performance status of 0–2. Topotecan was administered intravenously at 1.5 mg/m²/day for five days and repeated every 21 days. The major toxicity was hematologic with 19 out of 48 (40%) patients having grade IV granulocytopenia and 4 out of 48 (8%) patients demonstrating grade IV thrombocytopenia. Two patients (4%) demonstrated partial response. Thirty patients have died and the Kaplan-Meier estimate of median survival is 9 months (95% confidence interval; 7–16 months). Topotecan in this dose and schedule does not appear active in patients with advanced colorectal cancer.     

A phase II study of (2″ R)-4′ -0-tetrahydropyranyladriamycin (THP) in hematological malignancies

A phase II study of new anthracycline, THP, was conducted in 46 patients with hematological malignancies in a cooperative study. THP was given intravenously either at a dose of 13–34 mg/m² for 3–5 consecutive days or 35–50 mg/m² at 3–4 week intervals.Of 21 patients with acute leukemia, complete response (CR) was observed in 3 patients and partial response (PR) in 4. Of 22 patients with malignant lymphoma, CR was observed in 2 and PR in 6.The predominant toxicity was myelosuppression. Leukopenia was noted in 73% of patients and thrombocytopenia in 14%. Anorexia, nausea and vomiting were observed in 49%, 26% and 23%, respectively. Alopecia and acute cardiac toxicities were mild and recovered quickly on discontinuation of THP.Thus, THP was found to be effective for acute leukemia and malignant lymphoma.     

Phase II trial of vinblastine in advanced ovarian carcinoma

Summary A phase II trial of vinblastine in patients with refractory epithelial ovarian adenocarcinoma of the ovary was conducted by the Gynecologic Oncology Group (GOG) between March 9, 1988 and July 7, 1988. Vinblastine was administered in a dose of 9 mg/m² intravenously every three weeks until disease progression or toxicity supervened. Twenty patients were entered initially. One was ineligible due to a previous primary cancer. Thus, 19 patients are evaluable for toxicity and response. All patients had cisplatin-combination chemotherapy and four had prior radiotherapy. Median age was 63 years (range 40–75 years). Thirteen patients had disease in the pelvis and six had extrapelvic metastases. Ten patients had grade 3 lesions and seven had grade 2. A median of two courses (range: 1–6) were administered. Toxicity was moderate. Seven patients (36.8%) experienced GOG grade 3 or 4 leukocytopenia and six had grade 3 or 4 granulocytopenia. Median nadir WBC was 2,000 cells/1 (range 600–3,500) and platelet nadirs for the three patients with thrombocytopenia were 60,000, 116,000, and 147,000. Other toxicity included grade 3 gastrointestinal and renal toxicity in one patient each. Seven patients (36.8%) had stable disease on therapy and 12 had increasing disease. No responses were observed. Vinblastine in this dose and schedule is inactive in patients with resistant epithelial ovarian adenocarcinoma progressing on first-line chemotherapy. Responsible author: Dr. Gregory P. Sutton, Indiana University Medical Center, Section of Gyn. Oncology, Dept. of Obstetrics & Gynecology, 926 West Michigan Street, Indianapolis, IN 46223, USA.     

Adverse drug reactions related to drugs used in orthostatic hypotension: a prospective and systematic pharmacovigilance study in France

Objective The aim of the present study was to investigate and characterise adverse drug reactions (ADRs) to drugs used in France for orthostatic hypotension (OH).Methods In this prospective and systematic study, 121 consecutive out-patients suffering from primary (Parkinsons disease, pure autonomic failure, multiple system atrophy, Lewy bodies disease) or secondary (diabetic and non-diabetic peripheral neuropathies) autonomic failure with symptomatic OH requiring pharmacological treatment with at least one drug marketed in France for OH were included together with six patients with refractory neurocardiogenic syncope.Results Of the patients, 85 received a monotherapy—mainly with midodrine (49.4%)—and 42 received various combinations, the association of midodrine and fludrocortisone being the most frequent (66.6%). Of all the 127 patients, 88 suffered from a total of 141 ADRs (1.60 per patient) with no statistical difference in ADR frequency between monotherapy and drug combinations (P>0.05). Among ADRs, 24 (17.0%) were considered as serious and 16 (11.3%) were considered as unexpected, most of them observed with heptaminol.Conclusions This study shows a high frequency of ADRs (especially serious and unexpected ADRs) with antihypotensive drugs. It strongly suggests the need for a better evaluation of the safety profile of antihypotensive drugs and improvement in summary of product characteristics.     

Comparison of N-acetylcysteine and mesna as uroprotectors with ifosfamide combination chemotherapy in refractory germ cell tumors

From January 1983 through August 1988, 318 consecutive patients with refractory germ cell neoplasms were treated with ifosfamide-containing combination chemotherapy. The patients received ifosfamide at 1.2 gm/m² day with cis-platin 20 mg/m² day for 5 days and etoposide 75 mg/m² day for 5 days or vinblastine 0.11 mg/kg on days 1 and 2 for each cycle. Of 277 evaluable patients, NAC was used as an uroprotector in the initial 86 patients while the latter 191 consecutive patients received mesna to reduce urothelial toxicity. Dosages of NAC was 2.0 gm po q 6 hr and for mesna 120 mg/m² IV push prior to ifosfamide and then 1200 mg/m²/day as continuous infusion of 5 consecutive days. All patients received 3.0 liters of normal saline per day. The number of courses of chemotherapy given in the two groups were similar. Twenty-four of the 86 patients (27.9%) receiving NAC developed hematuria (13 patients — grade 1, 4 patients — grade 2, and 7 patients — grade 3 toxicity). While 8 out of 191 (4.2%) mesna patients developed hematuria (6 — grade 1 and 2 — grade 3) (p<0.0001). The incidence of severity of renal toxicity was similar in the two groups. Ifosfamide dosage was reduced solely for urothelial toxicity in 11 patients receiving NAC compared with none of the patients receiving mesna (p<0.0001). Chemotherapy response was similar in the two groups. In conclusion, mesna provides better urothelial protection from ifosfamide-induced toxicity than NAC and allows better maintenance of the drug dosage.     

原发性中枢神经系统淋巴瘤32例临床分析

目的 探讨原发性中枢神经系统淋巴瘤（PCNSL）临床特点、诊治方案及临床疗效。方法 回顾性分析1990年1月～2004年12月收治的PCNSL32例。结果 1例经立体定向活检确诊,31例手术确诊。31例手术中全切或近全切除28例（90％）,大部切除3例（10％）,无手术死亡病例。病理检查：B细胞型淋巴瘤30例,T细胞型淋巴瘤2例。术后临床症状改善22例（69%）,稳定6例（19％）,症状加重4例（12％）。术后辅以放射治疗25例,联合化疗9例。结论 PCNSL为少见恶性肿瘤,早期诊断,并进行有效的综合治疗是延长PCNSL患者生存期和改善生存质量的关键。     

Menogaril in the treatment of malignant mesothelioma: A phase II study

Summary Menogaril is a new semisynthetic anthracycline agent derived from the antitumor antibiotic Nogalomycin. Compared to doxorubicin it has similar or improved activity in anti-tumor cell line screening; human tumor cloning assays suggest modest anti-tumor activity as well. Menogaril is much less cardiotoxic than doxorubicin. We performed a phase II trial of this agent in 22 patients with advanced malignant mesothelioma. At a dose of 200 mg/m² iv every 4 weeks (160 mg/m² in previously radiated patients) only 1 of 22 (5%) evaluable patients had a partial remission lasting 4 months. (95% confidence limits 0.1–23%). The major toxic effects included pain at the site of infusion and granulocytopenia. While well tolerated, Menogaril has minimal activity in malignant mesothelioma. We do not plan further studies with Menogaril in this disease.     

Cisplatin,VP-16-213 and MGBG (Methylglyoxal bis guanylhydrazone) combination chemotherapy in refractory lymphoma,a phase II study

Summary In an effort to improve the treatment of patients with refractory or recurrent lymphoma, we developed a protocol using cis-platinum combined with two other agents of known efficacy in these disorders but with differing side effects: VP-16 and MGBG. Twenty-six eligible patients were treated with this regimen. There were 15 men and 11 women with a median age of 54 years (22–73), and performance status of 1 (0–3). Their diagnoses were Hodgkin's disease 5 and non-Hodgkin's lymphoma [NHL] 21 which included 11 with diffuse histocytic lymphoma [DHL]. The median number of chemotherapy regimens was 2 (1–5); 12 also received radiotherapy. Twenty patients are evaluable for response: 15 NHL and 5 Hodgkin's disease. Three patients, all of whom had DHL entered complete remission (20%) with a median time to treatment failure of 7 1/2 months. Six NHL (40%) and one Hodgkin's disease (20%) patients entered a partial remission. There were three early deaths: one due to progressive disease, one to acute respiratory failure, and one with disease status undocumented. Toxicity included leukopenia, thrombocytopenia, anorexia, nausea, vomiting, stomatitis, alopecia, renal failure, profound peripheral neuropathy, and hypersensitivity vasculitis. Treatment was stopped because of the latter two. These agents are non-crossresistant with doxorubicin-containing regimens. The drugs are possibly synergistic and modestly active with moderate to severe toxicity.     

氟达拉滨联合米托蒽醌与CHOP方案治疗恶性淋巴瘤的疗效及安全性

目的评价氟达拉滨联合米托蒽醌与CHOP方案治疗恶性淋巴瘤的疗效和安全性。方法 2010年2～11月收治经组织学确诊的恶性淋巴瘤40例患者,随机分为观察组及对照组,各20例,观察组接受含FND化疗,其中惰性淋巴瘤患者11例,复发的进展性淋巴瘤患者9例;对照组接受CHOP联合方案化疗,其中惰性淋巴瘤患者12例,复发的进展性淋巴瘤患者8例。结果观察组接受FND化疗的淋巴瘤患者有效率为90.0%,完全缓解率为60.0%,对照组接受CHOP方案化疗的淋巴瘤患者有效率为55.0%,完全缓解率为15.0%;观察组主要不良反应为骨髓抑制,有65.0%周期发生Ⅲ/Ⅳ度中性粒细胞减少,发生肺部感染3例;对照组无Ⅳ度中性粒细胞减少,仅20.0%周期发生Ⅲ度中性粒细胞减少,其他不良反应均为轻度,以消化道反应为主。结论含氟达拉滨联合米托蒽醌方案,对于恶性淋巴瘤患者具有肯定的疗效,不良反应可以耐受。     

Mitoxantrone,etoposide, mitoguazone and vinblastine chemotherapy (MV2) in relapsed and refractory lymphomas

Summary As part of a program to develop less leukemogenic chemotherapy regimens for the treatment of favorable prognosis Hodgkin's disease, a phase I–II trial of mitoxantrone, etoposide, mitoguazone, and vinblastine was used to treat patients with relapsed and refractory malignant lymphoma and Hodgkin's disease. An over-all partial response rate of 41% was observed. Although useful responses were seen, the absence of complete remissions is disappointing.Supported in part by a grant from the Mortimer Lacher Fellowship Fund.     

A phase II trial of pemetrexed in patients with metastatic renal cancer

Background. Metastatic renal cell carcinoma (RCC) is rising in incidence but remains difficult to treat. This clinical trial evaluated the effects of pemetrexed (multitargeted antifolate, ALIMTA®) for the treatment of metastatic RCC. Patients and methods. Patients were required to have histological diagnosis of metastatic RCC with measurable disease and no prior chemotherapy. In addition, patients were required to have a World Health Organization (WHO) performance status of 0–2 and adequate bone marrow reserve. Patients received pemetrexed at a dose of 600mg/m² as a 10min infusion every 3 weeks. Patients did not receive folic acid or vitamin B₁₂ supplementation. Results. Thirty-nine patients were enrolled and thirty two were evaluable for response. Three patients had a partial response for a response rate of 9% (95% CI 2–25%). The median time to progressive disease was 10.5 months. Of the nonresponders, twenty two had stable disease (median duration was 5.8 months; range 1.5–27.7) and seven had progressive disease (median time to progression was 5.4 months). Median time to progression for all qualified patients was 5.7 months. Common toxicities experienced were diarrhea and infection. Fatigue, stomatitis, and rash were also reported. The most common hematologic toxicity was grade 3/4 lymphopenia in 76% of patients. Leukopenia, granulocytopenia, and thrombocytopenia were also frequently reported. Conclusion. Single-agent pemetrexed has moderate activity in the treatment of metastatic RCC and should be investigated in combination with other potential active agents, as first-line treatment.     

盐酸氯丙嗪联合帕洛诺司琼预防化疗药物致恶心呕吐的临床观察

目的探讨盐酸氯丙嗪联合帕洛诺司琼预防化疗药物致恶心呕吐的临床疗效.方法 2014年1月—2014年7月在襄阳市中心医院行高致吐性化疗药物的住院患者126例,随机分为对照组和治疗组,每组63例.对照组患者在化疗第1天,开始化疗前30 min静脉滴注盐酸帕洛诺司琼注射液,0.25 mg/次,1次/d,注射时间30 s以上.治疗组在对照组基础上肌肉注射盐酸氯丙嗪注射液25 mg/次.3周为1个化疗周期,两组在1个化疗周期后观察恶心、呕吐的控制率.结果对照组和治疗组急性呕吐控制率分别为76.19%、84.13%,延迟性呕吐控制率分别为50.79%、63.49%,治疗组急性、延迟性呕吐控制率均显著高于对照组,两组比较差异具有统计学意义(P<0.05).对照组和治疗组急性恶心控制率分别为58.73%、77.78%,延迟性恶心控制率分别为 49.21%、65.08%,两组比较差异具有统计学意义(P<0.05).对照组和治疗组急性食欲减退控制率分别为87.30%、90.48%,延迟性食欲减退控制率分别为84.12%、87.30%,两组比较差异无统计学意义.结论 盐酸氯丙嗪联合帕洛诺司琼预防化疗药物致恶心呕吐具有较好的临床疗效,且不会增加不良反应,值得临床推广应用.     

Bcl-2、Ki-67和C-myc的表达与恶性淋巴瘤常规治疗后复发的关系

目的:研究Bcl-2、Ki-67和C-myc在恶性淋巴瘤(malignant lymphoma, ML)组织中的表达与常规化疗后复发的相关性.方法:采用免疫组织化学法检测65例行常规化疗的患者组织切片中Bcl-2、Ki-67和C-myc的表达.Bcl-2、Ki-67和C-myc不同表达患者的生存率统计采用Kaplan-Meier生存曲线和Log-rank检验.结果:Bcl-2表达与非霍奇金淋巴瘤(non-Hodgkin lymphoma,NHL)细胞来源有关,B细胞来源的NHL阳性率高于T细胞来源的NHL(P < 0.05),Ki-67、C-myc表达与NHL细胞来源、患者性别、年龄、临床分期和B症状等无关.C-myc的表达与常规化疗患者预后无关,Bcl-2阳性表达组和阴性表达组3年无病生存率分别为22.22%和55.56%,Ki-67阳性表达组和阴性表达组3年无病生存率分别为37.50%和61.54%,差异均有统计学意义(P < 0.05).结论:Bcl-2、Ki-67蛋白阳性表达的ML患者,常规化疗后易复发,应实施更加积极的治疗或造血干细胞移植.     

Phase II Trial of Liposomal Doxorubicin (Doxil®) in Advanced Soft Tissue Sarcomas

Purpose: To assess the objective response rate, toxicityexperienced, progression-free survival, and overall survival ofpatients with previously untreated advanced soft tissue sarcomastreated with a liposomal doxorubicin formulation (Doxil). Methods: Patients with metastatic or recurrent soft tissuesarcoma who had received no prior chemotherapy for advanceddisease were treated with liposomal doxorubicin (Doxil) accordingto a two stage accrual design. Doxil was administered at 50mg/m² every 4 weeks. A total of 15 patients were treated andare evaluable for response and toxicity. Results: The male/female ratio was 7/8, the median age was60 years (34–75) and the ECOG performance status was 0-1 in>90% of patients. Leiomyosarcoma (7/15) and malignant fibroushistiocytoma (2/15) were the most common histologic diagnoses.No objective responses were observed in the 15 evaluablepatients. No lethal toxicity occurred. Grade 3–4 leukopenia orneutropenia were reported in 3/15 (20%) patients. Grade 3mucositis or hand-foot syndrome occurred in 2/15 (13%) and 1/15(7%) patients respectively and seemed more severe in olderpatients. The median time to progression was 1.9 months (range0.9–6.2). Twelve patients have now died. The Kaplan-Meierestimate of median overall survival is 12.3 months. As called forin the study design, accrual was terminated because no responseswere obtained in the first 15 patients. Conclusion: Though well-tolerated, Doxil given accordingto this dose and schedule to patients with advanced soft tissuesarcoma had no significant therapeutic activity. A correlationbetween older age and skin/mucosal toxicity of Doxil is suggestedin this study but needs confirmation. Future investigations ofDoxil in soft tissue sarcomas should use a different schedule anddose.     

Phase I trial of intravenous carboplatin added to oral etoposide and oral cyclophosphamide for stage IV non-small cell lung cancer

The combination of oral etoposide and oral cyclophosphamide is an active and easily administered outpatient regimen for non-small cell lung cancer with leukopenia as the most common severe toxicity. To maintain ease of outpatient administration and to take advantage of a differing dose-limiting toxicity, we attempted to add escalating doses of intravenous carboplatin to full-dose oral etoposide and oral cyclophosphamide for chemotherapy-naive patients with Stage IV non-small cell lung cancer. The first 4 patients received etoposide and cyclophosphamide (each at 50 mg PO BID Days 1–12 every 28 days) with intravenous carboplatin on Day 1 at a dose calculated by the Calvert formula to achieve AUC 4. With this regimen dose-limiting toxicity (2 patients with Grade 4 leukopenia/granulocytopenia) was noted. An additional 3 patients therefore received etoposide and cyclophosphamide at a 25% reduced dose (each at 50 mg PO BID Days 1–9 every 28 days) with intravenous carboplatin on Day 1 at a dose calculated to achieve AUC 4. Dose-limiting toxicity (2 patients with Grade 4 leukopenia/granulocytopenia) was again noted. One patient achieved a partial response maintained for 6 months. However potentiation of leukopenia/granulocytopenia by carboplatin prevents full-dose use of either cyclophosphamide and etoposide or of carboplatin in this regimen.     

Phase II trial of CI-980 in patients with disseminated malignant melanoma and no prior chemotherapy. A Southwest Oncology Group study

Malignant melanoma is increasing infrequency at a rapid rate in the UnitedStates. Metastatic disease ischemoresistant with DTIC considered themost active single agent. CI-980 is asynthetic mitotic inhibitor that blocks theassembly of tubulin and microtubules. Ithas shown cytotoxic activity against abroad spectrum of murine and human tumorcell tines. CI-980 can cross the bloodbrain barrier, is effective when givenorally or parenterally, and is activeagainst multidrug resistant cell linesoverexpressing P-glycoprotein. In thistrial, patients with disseminated melanomawith measurable disease, SWOG performancestatus of 0–1, no prior chemotherapy orimmunotherapy for metastatic disease, andadequate hepatic and renal function, wereenrolled. Treatment with CI-980 was givenby 72 h continuous IV infusion at a doseof 4.5 mg/m²/day, days 1–3 every 21 days. Twenty-four patients were registered onthis study with no patients ineligible. They ranged in age from 33–78 withperformance status of 0 in 15 patients and1 in 9 patients. Nineteen patients hadvisceral disease with 12 having liverinvolvement. There were no confirmedresponses. The overall response rate was0% (95% CI 0%–14%). The medianoverall survival is eleven months (95% CI4–14 months). The most common toxicitieswere hematologic and consisted ofleukopenia/granulocytopenia and anemia,with nausea/vomiting andmalaise/fatigue/weakness also frequent. CI-980 administered at this dose andschedule has insufficient activity in thetreatment of disseminated malignantmelanoma to warrant furtherinvestigation.     

继发性B细胞型非霍奇金淋巴瘤患者的临床特征分析

目的　探讨继发于非血液系统恶性肿瘤的B细胞型非霍奇金淋巴瘤（sNHL）患者的临床特征及预后情况。方法　2007年1月—2018年5月就诊于我院的NHL患者中,1.65%（47/2 853）以第二恶性肿瘤的形式出现,其中44例为B细胞型sNHL。44例中第一原发恶性肿瘤治疗情况：29例为手术切除治疗,10例为手术联合化疗,2例为手术联合放疗,3例接受手术联合化疗及放疗。继发肿瘤的治疗情况：34例患者接受化疗,5例患者接受化疗+手术切除,4例患者因结外病变或巨大包块接受放疗,1例结外边缘区B细胞淋巴瘤,黏膜相关淋巴组织型淋巴瘤（胃型）患者仅接受抗幽门螺杆菌治疗。中位化疗时间为6（2,8）个月。CD20+的弥漫大B细胞淋巴瘤（DLBCL）或CD20+Ⅲ～Ⅳ期滤泡淋巴瘤（FL）患者在化疗前1 d静脉滴注利妥昔单抗（375 mg/m2）。中位随访时间11.4（4.2,28.8）个月。结果　44例sNHL患者最常见的第一原发恶性肿瘤疾病类型为乳腺癌（10例）,最常见的sNHL病理类型为DLBCL（29例）。65.9%（29/44）的患者第一原发肿瘤诊断年龄＜60岁,59.1%（26/44）的患者sNHL诊断年龄≥60岁。中位sNHL发生时间为63.4（25.2,146.9）个月。平均无疾病进展时间为9.6（4.1,26.0）个月。3年总生存率为73.5%。一线治疗后完全缓解率为38.6%,总缓解率为63.6%。利妥昔单抗组与未利用利妥昔单抗组的3年总生存率分别为81.1%和66.5%（Log-rank χ2=2.026,P＞0.05）。单因素分析显示第一原发恶性肿瘤诊断年龄≥60岁（Log-rank χ2=7.562,P＜0.05）,sNHL诊断年龄≥60岁（Log-rank χ2=4.887,P＜0.05）均提示预后不良;多因素分析显示第一原发恶性肿瘤发病年龄≥60岁（HR=4.745,95%CI：1.405～16.020）是影响sNHL患者生存率的独立危险因素。结论　第一原发恶性肿瘤的诊断年龄≥60岁会增加sNHL患者的死亡风险。