西妥昔单抗联合FOLFIRI 方案治疗晚期胃癌的疗效观察

目的:观察西妥昔单抗联合FOLFIRI方案用于一线治疗失败的局部晚期或转移性胃癌患者,观察其疗效和不良反应,并观察其与疗效和预后的相关性。方法:每2疗程评价肿瘤病灶情况,观察不良反应,随访肿瘤进展情况及生存期。按照实体瘤疗效评价标准(Response Evaluatione Criteria in solid Tumors,RECIST)进行肿瘤缓解评估,按照国立癌症研究所常见不良事件评价标准3.0版(NCI一CTCAE3.0)进行不良事件分级。计算肿瘤缓解率、中位至疾病进展时间和中位总生存期。结果:在38例至少完成了2个周期治疗并进行了疗效评价的患者中,观察到1例完全缓解(CR),占0.03%;13例部分缓解(PR),占34.00%;总的缓解率(ORR=CR+PR)为37.00%。疾病稳定(SD)的患者有20例,占53.00%;疾病控制率(Disease Control Rate,DCR=CR+PR+SD)为89.00%;疾病进展(PD)的患者为4例,占11.00%。本研究方案总体安全性良好,未发生一例治疗相关性死亡。其中III/IV度粒细胞减少的发生率为52.5%,粒缺性发热的发生率为13.1%,III/IV度度贫血的发生率为29.5%,III/IV度度血小板下降的发生率为8.2%。III/IV度非血液学毒性包括恶心(8.2%),呕吐(6.6%),口腔炎(1.6%),腹泻(6.6%),感染(4.9%),乏力(4.9%),肠梗阻(6.6%),转氨酶升高(l.6%),过敏反应(l.6%)和皮疹(9.8%)。结论:本研究显示在晚期胃癌患者的二线治疗中西妥昔单抗联合FOLFIRI是一个安全有效的方案,需要进一步的研究寻找有效的生物标记物。     

Gemcitabine-cisplatin combination in the first line treatment of non-small cell lung cancer. Our experience and analysis of safety

In our Department we have studied the first line treatment of 90 stage IIIA-IV non-small cell lung cancer patients using gemcitabine/cisplatin combination. Thirteen cases have been unevaluable for various reasons. At the time of evaluation the planned 4 cycles have been delivered to 38% of patients (34/90). The PR was 39% (30/77), the CR was 2.6% (2/77) while the ORR was found to be 41% (32/77). 226 treatment cycles have been evaluated for side effects. There was no treatment-induced death in this series. CTC grade 3-4 neutropenia occurred in 5.7% of the cycles and only in 2 cases combined with fever. CTC grade 3-4 thrombocytopenia occurred in 4.4% of the cycles but only one patient required platelet suspension administration. Grade 3-4 anaemia developed in 3.5% of the cycles where 5 cases have been treated with RBC concentrate while 3 cases with erythropoietin. Complete alopecia occurred in 6 patients but 3 of them received brain irradiation as well. CTC grade 3-4 nausea and vomiting occurred in 4.4 and 3% of the cycles, respectively, but rehydration was only necessary in 3% of the cycles. Delay of the therapy due to hematological toxicity or vomiting occurred in 8% of the cycles but did not last longer than 2 weeks. Severe CTC grade 3-4 nephrotoxicity did not occur in this study while grade 1-2 elevation of serum creatinine level was found in 1.7% of the cycles. We have concluded that the gemcitabine/cisplatin combination is a safe outpatient modality for the first line treatment of advanced non-small cell lung cancer patients.     

Carminomycin study in breast cancer]

Karminomycin was used for the treatment of cases with disseminated cancer of the mammary gland in doses of 5 mg/m2 of the body surface intravenously every day for 5 days (15 patients) or 6 mg/m2 twice a week for 2-3 weeks (30 patients). Partial remission or diminution of the tumor size at least by 50 per cent was observed in 26 and 17 per cent of the patients respectively. The remission duration was from 2 to 6 months. With the use of the shortperiod scheme the frequency of the direct side reactions increased. Leucopenia as a side effect was registered in 100 and 40 per cent of the patients and thrombocytopenia was registered in 18 and 3 per cent of the cases respectively.     

紫杉醇在治疗晚期或复发性宫颈癌中的应用分析

为了探讨紫杉醇在治疗晚期或复发性宫颈癌中的疗效和安全性,为不适合手术或者放射治疗的患者(包括晚期或复发性宫颈癌患者)注射紫杉醇170 mg/m^2、卡铂5 mg·mL^-1·min^-1、贝伐珠单抗12 mg/kg治疗,每20 d一次,并记录期间的不良反应,直至疾病有所缓解或其毒性有所限制。总共有38名患者接受了平均8个治疗周期(范围2~25),中期随访值为18.5个月(范围2~29)。结果显示,19名患者(50.0%)经历完全反应,而15名患者经历(39.4%)部分反应,平均持续时间为6个月。3级和4级血液学毒性表现为中性粒细胞减少症15例(39.4%)、白细胞减少症13例(34.2%)、贫血症13例(34.2%)、血小板减少症11例(28.9%)。1名接受过骨盆照射的患者发生了2级直肠阴道瘘。本研究表明,紫杉醇、卡铂和贝伐单抗的组合对于晚期或复发性宫颈癌患者是有效且安全的。     

Induction of tumor regression by administration of B7-Ig fusion proteins: mediation by type 2 CD8+ T cells and dependence on IL-4 production

CD28 signals contribute to either type 1 or type 2 T cell differentiation. Here, we show that administration of B7.2-Ig fusion proteins to tumor-bearing mice induces tumor regression by promoting the differentiation of antitumor type 2 CD8(+) effector T cells along with IL-4 production. B7.2-Ig-mediated regression was not induced in IL-4(-/-) and STAT6(-/-) mice. However, it was elicited in IFN-gamma(-/-) and STAT4(-/-) mice. By contrast, IL-12-induced tumor regression occurred in IL-4(-/-) and STAT6(-/-) mice, but not in IFN-gamma(-/-) and STAT4(-/-) mice. Moreover, B7.2-Ig treatment was effective in a tumor model not responsive to IL-12. B7.2-Ig administration elicited elevated levels of IL-4 production. Tumor regression was predominantly mediated by CD8(+) T cells, although the induction of these effector cells required CD4(+) T cells. Tumor regression induced by CD8(+) T cells alone was inhibited by neutralizing the IL-4 produced during B7.2-Ig treatment. Thus, these results indicate that stimulation in vivo of CD28 with B7.2-Ig in tumor-bearing mice results in enhanced induction of antitumor type 2 CD8(+) T cells (Tc2) leading to Tc2-mediated tumor regression.     

Subcutaneous interleukin-2 and interferon-alpha 2b in patients with metastatic renal cell cancer: the German outpatient experience

A phase II clinical trial was conducted using subcutaneous recombinant human interleukin-2 (rIL-2, EuroCetus) and subcutaneous interferon-alpha 2b (rIFN-alpha 2b, Essex) in patients with advanced cancer. Safety and tolerance of this outpatient regimen were assessed in 17 patients with progressive metastatic renal carcinoma, 14 of whom were evaluable for clinical response to combined rIL-2 and rIFN-alpha 2b. In this study, rIL-2 was administered every 12 hours, at 1.5 million (Cetus) U/m2 on days 1 and 2, followed by 0.3 million U/m2 5 days per week for 6 consecutive weeks. Concomitantly, rIFN-alpha 2b was given as 5 million U/m2 three times weekly for 6 consecutive weeks. Patients presenting with stable or regressive disease after 6 weeks of rIL-2 and rIFN-alpha 2b (11 of 14) were scheduled to repeat combination therapy. After one treatment cycle, five of 14 patients presented with partial remission; two of these patients achieved complete regression of metastatic lesions. After therapy, six patients have been in stable disease for up to 8 months. toxicity of this regimen was moderate, with local inflammation of the injection sites, grade I-II (World Health Organization criteria) fevers, chills, malaise, nausea and/or vomiting, and anorexia in 70% to 100% of patients treated. After 6 weeks of rIL-2 and rIFN-alpha 2b, laboratory evidence of treatment-related hypothyroidism and hyperthyroidism was obtained in one and four patients, respectively. Immunogenicity of sc rIL-2 was mostly limited to the development of nonneutralizing antibodies that occurred in approximately 40% of patients. None of the patients exhibited antibodies specific to rIFN-alpha 2b.     

Aromatase inhibitors in the treatment of breast cancer

A number of inhibitors of estrogen synthesis are now becoming available which could be of value in the treatment of breast cancer. 4-Hydroxyandrostenedione (4-OHA), the first of these compounds to enter the clinic has been found to be effective in postmenopausal patients who have relapsed from tamoxifen. Thus, in studies of 240 patients, 26% patients experienced partial or complete response to treatment. An additional 25% patients had disease stabilization. 4-OHA is a potent selective, steroidal inhibitor which causes inactivation of aromatase in vitro. It is effective in reducing concentrations of ovarian estrogens in rats and of ovarian and peripheral estrogens in non-human primate species. The compound has been shown to lower serum estrogen levels in postmenopausal breast cancer patients. However, not all of these patients experienced disease remission, suggesting that their tumors were hormone insensitive rather than that the dose of 4-OHA was suboptimal. In trials of patients who had not received prior tamoxifen treatment, 4-OHA (250 mg i.m. every 2 weeks) was found to induce complete or partial tumor regression in 33% of patients. The response of patients was not significantly different from that observed in patients treated with tamoxifen (30 mg o.d) of 37%. No significant difference between treatments was observed for disease stabilization, the duration of response or median survival. Several other steroidal aromatase inhibitors have been studied, such as 7-substituted androstenedione derivatives. MDL 18962 [10-(2-propynyl)estr-4-ene-3,17-dione] and FCE 24304 (6-methylen-androsta-1,4-diene-3,17-dione) are currently in clinical trials. Non-steroidal inhibitors of cytochrome P-450 enzymes, such as imidazole and triazole derivatives have been developed which are highly selective for aromatase. Three triazoles which are very potent and selective inhibitors are vorazole (6-[(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)-methyl]1-methyl-1H-benzotriazole R 76713, arimidex 2,2′[5-( -1,2,4-triazol-1-yl methyl)-1,3-phenylene]bis(2-methylpropiononitrile) (ZD1033) and letrozole 4-[1-(cyanophenyl)-1-(1,2,4-triazolyl)methyl]benzonitril (CGS 20267). These compounds reduce serum estradiol concentration to undetectable levels in breast cancer patients. These highly potent inhibitors provide the opportunity to determine whether a further degree of estrogen suppression will be important in producing greater clinical response. With the recent approval of 4-OHA in several countries and the introduction of the potent new compounds, aromatase inhibitors either alone or in combination with the antiestrogen are likely to improve the treatment of breast cancer.     

Experiences in the treatment of tumour of base of the tongue with high dose rate interstitial radiotherapy on the basis of a retrospective analysis

PURPOSE: To describe the role, the execution and the importance of interstitial radiotherapy in the irradiation of the base of tongue cancer. MATERIAL AND METHODS: Between January, 1993 and December, 1998 nineteen patients with primary squamous cell cancer of the base of tongue (1 T1N0, 3 T2N0, 2 T3N0, 2 T3N2, 3 T4N0, 6 T4N1, 2 T4N2) were managed with brachytherapy partly with definitive intention combined with teletherapy (60-66 Gy) as a boost, partly as a single postoperative treatment. Irradiation was carried out by HDR after-loading (Ir-192) unit, using rigid needle or flexible plastic catheter. The treatment plan was made by PLATO 3D brachytherapy planning system. In case of boost the mean total dose of brachyherapy was 22 Gy (12-30 Gy), in postoperative treatment it was 27 Gy (24-30 Gy). RESULTS: 6-8 weeks after the definitive radiotherapy the CT/MR showed complete remission in 67% and partial remission in 33% of the patients. Of all treated patients during the mean follow-up period (30 months) the local tumour control was 42%. Five patients (26%) died in local failure. Six patients (32%) are alive with tumour. Osteoradionecrosis and fistula did not occur. CONCLUSIONS: In the oncological treatment of the advanced base of tongue tumour the combination of percutan and interstitial radiotherapy seems to be very advantageous,because it improves not only the curability, but the patients' quality of life as well.     

Aromatase and other inhibitors in breast and prostatic cancer

Estrogens have an important role in the growth of breast and other hormone-sensitive cancers. We have shown that 4-hydroxyandrostenedione (4-OHA) selectively blocks estrogen synthesis by inhibiting aromatase activity in ovarian and peripheral tissues and reduces plasma estrogen levels in rat and non-human primate species. In postmenopausal men and women, estrogens are mainly of peripheral origin. When postmenopausal breast cancer patients were administered either by daily oral or parenteral weekly treatment with 4-OHA, plasma estrogen concentrations were significantly reduced. Complete or partial response to treatment occurred in 34% of 100 patients with advanced breast cancer, while the disease was stabilized in 12%. We recently studied the effects of 4-OHA and other aromatase inhibitors, 10-propargylestr-4-ene-3,17-dione (PED) and imidazo[1,5-]3,4,5,6-tetrahydropyrin-6-yl-(4-benzonitrile) (CGS 16949A) as well as 5-reductase inhibitors, N,N-diethyl-4-methyl-3-oxo-4-aza-5-androstane-17β-carboxyamide (4-MA) and 17β-hydroxy-4-aza-4-methyl-19norandrost-5-en-3-one (L651190) in prostatic tissue from 11 patients with prostatic cancer and six patients with benign prostatic hypertrophy (BPH), and from normal men at autopsy. We attempted to measure aromatase activity in tissue incubation by quantitating ³H₂O released during aromatization of androstenedione or testosterone labeled at the C-1 position. The amount of ³H₂O released from all samples was at least twice that of the heat inactivated tissue samples. The ³H₂O release was significantly inhibited by 4-OHA and 4-MA, but not by the other aromatase inhibitors. However, when HPLC and TLC were used to isolate steroid products, no estrone or estradiol was detected in the incubates. Furthermore, no aromatase mRNA was detected following amplification by PCR. The 4-OHA was found to inhibit 5-reductase in both BPH and cancer tissue, although to a lesser extent than 4-MA. The other aromatase inhibitors were without effect. Although a mechanism involving intraprostatic aromatase is not likely, inhibitors may act to reduce peripherally-formed estrogens. In postmenopausal breast cancer, the results indicate that 4-OHA is of significant benefit.     

Multiple cycles of constant infusion recombinant interleukin-2 in adoptive cellular therapy of metastatic renal carcinoma

Twenty patients were treated with metastatic renal cell cancer with 5-day cycles of constant infusion recombinant interleukin-2 (rIL-2) at 3 X 10(6) U/m2/day and with infusion of in vitro activated autologous mononuclear cells. The initial eight patients completed all rIL-2 and cellular therapy in a single 25-day treatment period. The subsequent 12 patients entered a 6-month treatment program involving two separate 15-day cycles of cellular therapy followed by four monthly cycles of maintenance rIL-2. Among eight patients in the 25-day treatment program, there were two with partial response (PR) and one with minor response (MR). None of these responses exceeded 2 months in duration. Among the 12 patients undergoing recycling of therapy, there were two with complete response (CR), two with PR, and one with MR. All four patients with CR or PR in this group demonstrated continuing response with recycling of treatment and none relapsed while receiving maintenance interleukin-2. Three remain in remission at 10, 11, and 12 months. These pilot data confirm that patients can tolerate multiple cycles of adoptive immunotherapy involving constant infusion rIL-2 and suggest that recycling of therapy is necessary to achieve clinically meaningful results.     

Beneficial effects of high daily dose bromocriptine treatment in Cushing's disease.

Treatment with a high daily dose bromocriptine was evaluated in 6 Cushing's disease patients (4 females and 2 males; aged 23 to 56 years). The highest doses administered were 40 mg to patient 1, 55 mg to patient 2, 35 mg to patient 3, 25 mg to patient 4, 25 mg to patient 5, and 17.5 mg to patient 6. The former 3 cases, 2 (patients 1 and 2) of whom were previously reported and further followed up, showed clinical and biochemical improvement with the regimen. Patient 1 who obtained remission with 40 mg/day has been on remission for further 14 months with a total of 36 months. Patient 2, who had a reduction in pituitary tumor size with 35 mg daily, relapsed thereafter. The therapy, however, resolved the paradoxical responses of plasma ACTH and cortisol to arginine. Readministration of bromocriptine resulted into another clinical and biochemical improvement with 45 to 55 mg/day. Patient 3, a relapsed case after a remission with reserpine plus pituitary irradiation, showed an improvement in the 24-h urinary free cortisol excretion with 35 mg/day. Patient 4 was the only case who had a marked decrease in plasma cortisol (basal; 16.3, nadir; 1.9 micrograms/dl) after a single-dose bromocriptine test among the 5 cases tested. The patient had favorable response with 25 mg/day for 2 months but the dose was not increased after an escape. Patient 5 received the drug in 4 occasions, 7.5 to 25 mg/day, in combination with several agents, which failed to induce clinical remission. The last patient did not respond to a maximum dose of 17.5 mg/day. These observations suggest that, regardless of the result of a single-dose bromocriptine test, treatment with a high daily dose of bromocriptine, 35 mg or more, may be necessary to obtain a favorable clinical response and normal cortisol secretion.     

CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1 and GSTT1 polymorphisms or their combinations are associated with the increased risk of the laryngeal squamous cell carcinoma

Polymorphisms in the selected genes controlling carcinogen metabolism (CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1, GSTT1) considered separately or in different combinations, were investigated for an association with tobacco smoke-associated squamous cell carcinoma (SCC) of the larynx. The case-control study was performed in 289 patients with laryngeal SCC and in 316 cancer-free controls; all were Caucasian males from the same region of Poland and current tobacco smokers. The DNA samples were genotyped using PCR-RFLP and multiplex PCR. The variants' frequencies in both groups were compared; odds ratios and their 95% confidence intervals were calculated by logistic regression analyses. The CYP1A1*1/*4, CYP2D6*4/*4, NAT2*4/*6A genotypes, as well as the CYP1A1*4, CYP2D6*4 and NAT2*4 alleles, were found at significantly higher frequencies in cases than in controls indicating their role as "risk-elevating" factors in laryngeal SCC. Combined genotypes, characterized by the presence of the "risk-elevating" variants at more than one locus, often occurred together with the null variant of the GSTM1 gene and homozygous XPD A/A (Lys751Gln, A35931C) genotype. Furthermore, we identified some "protective" variants, found more frequently in controls than in cases, i.e. the NAT2*6A/*6A and NAT2*5B/*6A genotypes. A distribution of "risk" or "protection" genotypes/alleles seems to be connected with age as an occurrence or risk genes was more frequent in the group of "young" cases (< or = 49 years). Accumulation of certain alleles or genotypes of the CYP1A1, NAT2, GSTM1 and XPD seems to be associated with either increased or decreased risk to develop laryngeal SCC. Therefore, polymorphisms in these genes may play a role in the laryngeal cancer etiology.     

The early treatment results of well differentiated thyroid cancer and its dependence on chosen factors

INTRODUCTION: The aim of the study was to estimate the influence of a thyroid remnants' volume, postsurgical concentration of thyroglobulin and radioiodine dose on the early treatment efficacy of well differentiated thyroid cancer. MATERIAL AND METHODS: We retrospectively analyzed 91 patients (76 females, 15 men) with well differentiated thyroid cancer. RESULTS: Histological classification revealed 68.1% (62/91) papillary thyroid cancers, 25.3% (23/91) follicular thyroid cancers, and 6.6% (6/91) oxyphilic thyroid cancers. Among the group, 74 (81.3%) patients reached the remission criteria and the remaining 17 patients (18.7%) showed biochemical and morphological evidence of metastatic disease. The remission was obtained in 100% of patients in stage I of the disease, 68.4% - in stage II, 78.6% - in stage III and 33.3% in stage IV. The total radioiodine dose used in patients with remission, did not differ from the dose used in patients without remission. We did not observe the influence of remnant's volume on treatment efficacy, however larger remants required higher dose of radioiodine to obtain the remission. Patients with remission had lower postsurgical thyroglobulin concentration than patients without remission. (22.2 vs. 103.3 ng/ml; p = 0.00025). CONCLUSIONS: Early treatment results of well differentiated thyroid cancer depend on the clinical stage, and postoperative serum thyroglobulin level measured after endogenous TSH stimulation. Early treatment results are not dependent on age, sex, histological type of thyroid cancer, the dose of radioiodine used in brackets of 60-150 mCi and additional diseases. Total thyroidectomy is equally efficient as near total.     

Aromatase and its inhibitors--an overview

Estrogen synthesis by aromatase occurs in a number of tissues throughout the body. Strategies which reduce production of estrogen offer useful means of treating hormone-dependent breast cancer. Initially, several steroidal compounds were determined to be selective inhibitors of aromatase. The most potent of these, 4-hydroxyandrostenedione (4-OHA) inhibits aromatase competitively but also causes inactivation of the enzyme. A number of other steroidal inhibitors appear to act by this mechanism also. In contrast, the newer imidazole compounds are reversible, competitive inhibitors. In vivo studies demonstrated that 4-OHA inhibited aromatase activity in ovarian and peripheral tissues and reduced plasma estrogen levels in rat and non-human primate species. In rats with mammary tumors, reduction in ovarian estrogen production was correlated with tumor regression. 4-OHA was also found to inhibit gonadotropin levels in animals in a dose-dependent manner. The mechanism of this effect appears to be associated with the weak androgenic activity of the compound. Together with aromatase inhibition, this action may contribute to reducing the growth stimulating effects of estrogen. A series of studies have now been completed in postmenopausal breast cancer patients treated with 4-OHA either 500 mg/2 weeks or weekly, or 250 mg/2 weeks. These doses did not affect gonadotropin levels. Plasma estrogen concentrations were significantly reduced. Complete or partial tumor regression occurred in 26% of the patients and the disease was stabilized in 25% of the patients. The results suggest that 4-OHA is of benefit to postmenopausal patients who have relapsed from prior hormonal therapies. Several of the steroidal inhibitors are now entering clinical trials as well as non-steroidal compounds which are more potent and selective than aminoglutethimide. Aromatase inhibitors should provide several useful additions to the treatment of breast cancer.     

Zoledronic Acid Therapy of Patients With Paget Disease of Bone Resistant to or With Unsustained Remission Following Prior Bisphosphonate Therapy

Objective: To evaluate the effect of zoledronic acid (ZA) in patients with Paget disease (PD) who had not had a biochemical remission with prior bisphosphonate therapy or had a remission ≤12 months.Methods: The effects of ZA therapy were studied in 14 patients aged 54 to 90. Serum alkaline phosphatase (ALP) levels were elevated to at least 40% above the normal reference range, and glomerular filtration rates (GFRs) were ≥40 mL/minute. ZA (5 mg) was infused over 15 minutes. ALP and urine N-telopeptide/creatinine (NTx/Cr) were obtained before therapy and at 3, 6, 9, and 12 months, and thereafter at 4-month intervals.Results: At baseline, ALP ranged from 141 to 1,009 U/L. In 13 patients, ALP fell to normal following ZA administration. Remissions occurred in 9 patients who had not previously had a remission. Remissions varied from 12 to 60 months and were more prolonged in 4 patients with prior remissions ≤12 months. ZA failed to induce a remission in 1 patient. Ten to 12 days after therapy in 3 asymptomatic patients, serum calcium levels fell to 7.9, 8, and 8.3 mg/dL. Other than flu-like symptoms in 3 patients after ZA infusion, there were no other adverse effects.Conclusion: Therapy with ZA induced remissions in 13/14 patients and induced more prolonged remissions in patients who previously had remissions ≤12 months. The lack of remission in 1 patient despite 2 courses of therapy is evidence of a continuing therapeutic challenge for some patients with a more resistant form of PD.Abbreviations: ALP = alkaline phosphatase Cr = creatinine NTx = N-telopeptide 25-OHD = 25-hydroxyvitamin D PD = Paget disease ZA = zoledronic acid     

Squamous cell carcinoma antigen for monitoring cervical cancer

The tumour-associated antigen was determined in the plasma of patients with squamous cell carcinoma (SCC) of the uterine cervix by radioimmunoassay. Setting a limit of 2 ng/ml, levels were abnormal in 13.4% of healthy controls, in 14% of patients with carcinoma in situ and in 62% of patients with invasive cervical SCC. The incidence of elevated SCC antigen levels and the absolute antigen plasma concentration were dependent upon the tumour load, increasing significantly with advanced stage disease. Abnormal SCC antigen values in operable cervical cancer declined to normal within one week after radical hysterectomy with pelvic lymphadenectomy. In cases of radiotherapy antigen values took 4-6 weeks after the start of treatment to return to normal. The success of both treatment modalities was announced by an early rise in the SCC antigen in the initial phase of therapy, followed by normalisation. After successful primary treatment and a complete remission during further follow-up SCC antigen in plasma was only increased in 3.8% of the cases. Retrospective evaluations in ten patients with progressive disease showed the reappearance of abnormal SCC titers and further increase preceeding the clinically detectable relapse or progression, with a median interval of 8 weeks. The present study indicates that SCC antigen determination is not useful for the early diagnosis of cervical cancer, but it is a potential means for monitoring the efficacy of individual anticancer therapy of SCC of the uterine cervix and for detecting recurrent disease.     

Treatment results of nine patients with Burkitt's lymphoma

From 6/79 until 2/86, 9 patients (median age 39) with Burkitt's lymphoma were treated. Stage D disease was seen in 7 cases, stage C in two and stage A in one. The main symptom was abdominal pain or a rapidly progressing abdominal tumor. Three patients had bone marrow involvement and two had a Burkitt's leukemia. Three had typical chromosomal aberrations. Therapy consisted of a variety of chemotherapy regimens plus additional radiotherapy and/or bulk surgery. Two patients achieved complete remissions (of 6 and 20+ months duration), and 4 partial remissions were obtained. The remaining patients had either progressive, drug resistant disease or died early. One patient is currently alive and in complete remission at 20+ months. A second patient is alive at 20+ months in partial remission with traces of IgM-paraprotein still detectable. The main causes of death were tumor-lysis syndrome (4 patients) and therapy related sepsis with progressive tumor (3 patients). This poor outcome is probably due to a high proportion of high-risk patients and suboptimal therapy for this rapidly proliferating tumor.     

Hematopoietic stem cell transplantation for uncommon immune-mediated neurological disorders: A literature review

BackgroundChronic inflammatory demyelinating polyneuropathy (CIDP), stiff-person syndrome (SPS), neuromyelitis optica spectrum disorders (NMOSD) and severe refractory myasthenia gravis (MG) are immune-mediated neurological diseases that severely affect patients’ functionality and quality of life, with a considerable percentage undergoing relapse or not responding to conventional treatment options. Autologous hematopoietic stem cell transplantation (auto-HSCT) has emerged as a potential second-line treatment alternative.MethodsWe performed a literature review in PubMed/Medline, EMBASE, Web of Science and Cochrane Library from inception to September 2021 of reported cases and studies of CIDP, SPS, NMOSD and MG that underwent HSCT as a treatment option.ResultsA total of 173 patients who underwent HSCT were found, including 32 patients described in case reports and 60 in a phase 2 clinical trial with CIDP, 29 patients with SPS, 42 patients with NMOSD and 10 patients with refractory MG. Complete remission was documented in 68/92 patients with CIDP, 13/29 with SPS and 10/10 with MG. From the NMOSD cases, 24/42 were relapse-free at last follow-up, with 13/33 having negative anti-AQ4 antibodies after HSCT. From all the included studies, only 8/173 patients received an allogeneic HSCT, 4/8 after a failed auto-HSCT. All showed clinical improvement and disease remission.ConclusionHSCT has the potential to induce long-term remission in patients with CIDP, NMOSD, SPS or MG with adequate safety and tolerability. Collaboration between centers is needed to implement larger, homogeneous prospective studies, focusing on immunological correlates of favorable long-term response.     

解毒颗粒联合阿帕替尼治疗中晚期肝癌的回顾性研究

目的:评估解毒颗粒联合阿帕替尼治疗中晚期肝癌患者的疗效及其不良反应。方法:对2018年12月至2019年6月收治于海军军医大学第一附属医院口服解毒颗粒联合阿帕替尼的27例肝癌患者的临床资料进行回顾性研究。无法切除或复发的中晚期肝癌患者被纳入研究,给予解毒颗粒联合阿帕替尼治疗直至疾病进展或不可耐受其毒副反应,随访观察治疗效果、生存期、炎症因子指标及不良反应。结果:治疗后完全缓解(CR)4例(14.81%),部分缓解(PR)4例(14.81%),稳定(SD)8例(29.63%),进展(PD)11名患者(40.74%),疾病控制率(DCR)为59.26%(16/27),客观缓解率(ORR)为29.63%(8/27)。中位无进展生存期(PFS)为3.630个月,中位总生存期(OS)为13.667个月。常见的不良反应是高血压59.26%(16/27)、蛋白尿59.26%(16/27)、腹泻74.07%(20/27)以及手足综合征62.96%(17/27)。治疗后炎症因子指标中C反应蛋白、白介素2水平下降,存在统计学差异(P0.05)。结论:解毒颗粒联合阿帕替尼治疗中晚期肝癌安全、有效,可降低患者炎症反应,不良反应可耐受。     

Correlation of eosinophilia with clinical response in patients with advanced carcinoma treated with low-dose recombinant interleukin-2 and mitomycin C

Summary On the basis of our clinical findings that the ability of cancer patients to generate lymphokine-activated killer cells became markedly augmented after mitomycin C administration, we designed a treatment regimen comprising mitomycin C 12 mg/m², i.v. on day 1 and recombinant interleukin-2 700 U/m² (8000 IU/kg), i.v. every 12 h from day 4 through day 8. The treatment course was repeated at almost 7-day intervals. Altogether 33 patients with advanced carcinoma, including mainly gastrointestinal carcinoma, were treated with this regimen. Of these, 10 had a partial response (PR) and 4 had a minor response (MR). Since eosinophil counts peaked 1 day after either the first or second course of the therapy, the posttreatment values were compared to each pretreatment level, with regard to the clinical antitumor response to this treatment. When patients who showed PR were defined as responders, absolute eosinophil counts and the percentages of eosinophils in responders after both the first and second courses of the therapy were significantly greater than each pretreatment value or the posttreatment level in nonresponders. Further, these findings were almost identical, when both PR and MR were considered to be a true remission and therefore patients who exhibited PR or MR were defined as responders, although the difference between posttreatment levels of eosinophils in responders and nonresponders was not significant at the second course. These results indicate that eosinophilia induced by this treatment correlates with the clinical response to this therapy.