Ifosfamide,carboplatin, and etoposide for neuroblastoma

BACKGROUND:

The authors report a retrospective analysis of high‐dose ifosfamide, carboplatin, and etoposide (HD‐ICE) for patients with refractory or relapsed neuroblastoma (NB). A major reason for using this regimen was the long time since patients received previous treatment with a platinum compound. The authors also summarized the published experience on ICE in patients with NB.

METHODS:

Treatment comprised ifosfamide (2000 mg/m² daily for 5 days), carboplatin (500 mg/m² daily for 2 days), and etoposide (100 mg/m² daily for 5 days). Patients who had poor hematologic reserve (platelet count <100,000/μL) from previous therapy received peripheral blood stem cells (PBSCs) after HD‐ICE. Disease status before and after HD‐ICE was defined according to International Neuroblastoma Response Criteria (expanded to include ¹²³I‐metaiodobenzylguanidine findings). Publications that were informative about ICE for NB were reviewed.

RESULTS:

Seventy‐four patients received 92 cycles of ICE, including 37 patients who received PBSC rescue. Grade 3 toxicities were rare: 1–3 patients had encephalopathy, mucositis, or gastroenteritis. Bacteremia was documented in 24 of 92 cycles (26%). The absolute neutrophil count reached 500/μL on day 17–30 (median, day 22) in patients who had satisfactory hematologic reserve. Disease regressions (major and minor responses) were achieved by 14 of 17 patients (82%) with a new relapse, 13 of 26 patients (50%) with refractory NB, and 12 of 34 patients (35%) who were treated for progressive disease during chemotherapy (P = .005). In the literature, patients received ICE at lower dosages and achieved major response rates >36% in phase 1 and 2 studies (in which less comprehensive staging evaluations were used) that involved resistant NB and >70% in induction for newly diagnosed NB.

CONCLUSIONS:

HD‐ICE is appealing as salvage treatment or consolidative therapy because of its anti‐NB activity and the low risk of major nonhematologic toxicity. PBSC support is unnecessary for patients who had intact hematologic reserve. Cancer 2013. © 2012 American Cancer Society.     

星形细胞瘤的个体化治疗:显微手术、放疗、化疗及其疗效

背景与目的:星形细胞瘤是神经系统最常见的难治性肿瘤,约占神经上皮肿瘤的75%,具有发生率高、残废率高、复发率高和治愈率低的特点.对星形细胞瘤规范的个体化综合治疗是提高其疗效的希望和努力方向.本研究对62例星形细胞瘤患者行个体化显微手术治疗,术后依据肿瘤特点和病理级别行个体化辅助放/化疗,以探讨个体化综合治疗星形细胞瘤的效果.方法:研究组62例星形细胞瘤患者采用个体化治疗方案:(1)个体化显微手术;(2)个体化放疗;(3)个体化化疗(参考药敏实验).对照组50例星形细胞瘤患者治疗模式为:常规手术+局部外放疗+BCNU化疗.研究组62例患者术后病理学诊断为星形细胞瘤Ⅱ级19例、Ⅲ级32例、Ⅳ级11例;接受局部外放疗59例、接受化疗46例.对照组50例患者术后病理学诊断为星形细胞瘤Ⅱ级13例、Ⅲ级28例、Ⅳ级9例;接受BCNU化疗+局部外放疗的31例、接受局部外放疗+BCNU化疗的19例.平均随访25.8月,以影像学结果、KPS评分和生存率判定两组患者的疗效.结果:研究组肿瘤全切率为67.7%,对照组肿瘤全切率为58.0%;采用两种治疗模式治疗后低级别星形细胞瘤患者的KPS评分和生存率无显著差异;高级别星形细胞瘤采用个体化治疗模式显著改善了患者的生存,2年预期生存率研究组Ⅲ级为93.7%,Ⅳ级为36.3%;对照组Ⅲ级为67.5%,Ⅳ级为22.2%;研究组高级别星形细胞瘤的生存率显著高于对照组(P＜0.05).特别是Ⅳ级星形细胞瘤,研究组中位生存时间18.7个月,对照组中位生存时间12.8个月,两组有显著性差异(P＜0.01).结论:个体化显微手术可提高星形细胞瘤的全切除率,为手术后辅助治疗创造有利条件;个体化放/化疗可增加治疗的针对性,避免无效或有害的辅助治疗;个体化治疗方案可提高星形细胞瘤、特别是恶性星形细胞瘤的治疗效果.     

Carcinogenicity of benzidine, N, N'-diacetylbenzidine, and N-hydroxy-N, N'-diacetylbenzidine for female CD rats

To evaluate the role of metabolism in benzidine (BZ) carcinogenesis,BZ and 2 of its metabolites, N, N'-diacetylbenzidine and N-hydroxy-N,N'-diacetylbenzidine (NOHDABZ), were given by i.p. injectionto female CD rats twice weekly for 4 weeks beginning at 30 daysof age. A preliminary dose-response test showed that NOHDABZwas the most toxic compound; it caused chemical peritonitisand death in each of 4 animals given 70 µmol/kg body weight/injection.Toxicity was low in a 46-week carcinogenicity test which usedeither 10 or 30 µmol of each compound/kg body weight/injection;of 30 treated animals per group, the effective number of ratswas at least 28 per group. In the high dose BZ rats, the incidencesof mammary gland and Zymbal's gland tumors were 41% (fibroadenomaplus adenocarcinoma) and 21% (adenoma plus carcinoma), respectively,and these incidences were significantly greater than those incontrol animals. The metabolites were approximately equipotentwith BZ in mammary and Zymbal's gland, but the amount of NOHDABZactually reaching these organs may have been diminished by localreactions of NOHDABZ within the peritoneum. Thus, of 60 NOHDABZ-treatedrats, there were 2 toxicity-related early deaths, 6 rats withadhesions between visceral organs, and 5 tumors in tissues exposeddirectly to the compound. Since these effects were not presentin other treatment groups, NOHDABZ may represent an activatedcarcinogenic form of BZ.     

Nanotechnology for sensing, imaging, and treating cancer

Nanotechnology encompasses the creation and use of materials, devices, and systems at the level of atoms, molecules, and supramolecular structures. Nanotechnology for cancer consists of three main areas: (1) nanodetectors for sensing proteins and cancer cells, (2) nanoparticle or nanovector formulations for high-contrast imaging, and (3) nanotechnology-based drug delivery and therapeutic formulations. Although there are tremendous challenges facing nanotechnologists, nanotechnology, if properly integrated with established cancer research, can make laboratory-to-clinic transfer of technology successful, which can result in breakthrough potential for patient care.     

Thermal thresholds for teratogenicity,reproduction, and development

The human embryo and foetus may be especially vulnerable to chemical and physical insults during defined stages of development. In particular, the scheduled processes of cell proliferation, cell migration, cell differentiation, and apoptosis that occur at different times for different organ structures can be susceptible to elevated temperatures. With limited ability to regulate temperature on its own, the developing embryo and foetus is entirely dependent upon the mother's thermoregulatory capacity. As a general rule, maternal core body temperature increases of ～2°C above normal for extended periods of time, 2–2.5°C above normal for 0.5–1?h, or ≥4°C above normal for 15?min have resulted in developmental abnormalities in animal models. Significant differences in thermoregulation and thermoneutral ambient temperatures make direct extrapolation of animal data to humans challenging, and the above temperatures may or may not be reasonable threshold predictions for adverse developmental effects in humans. Corresponding specific absorption rate (SAR) values that would be necessary to cause such temperature elevations in a healthy adult female would be in the range of ≥15?W/kg (whole body average or WBA), with ～4?W/kg required to increase core temperature 1°C. However, smaller levels of thermal stress in the mother that are asymptomatic might theoretically result in increased shunting of blood volume to the periphery as a heat dissipation mechanism. This could conceivably result in altered placental and umbilical blood perfusion and reduce heat exchange with the foetus. It is difficult to predict the magnitude and threshold for such an effect, as many factors are involved in the thermoregulatory response. However, a very conservative estimate of 1.5?W/kg WBA (1/10th the threshold to protect against measurable temperature increases) would seem sufficient to protect against any significant reduction in blood flow to the embryo or foetus in the pregnant mother. This is more than three times above the current WBA limit for occupational exposure (0.4?W/kg) as outlined in both IEEE C95.1-2005 and ICNIRP-1998 international safety standards for radiofrequency (RF) exposures. With regard to local RF exposure directly to the embryo or foetus, significant absorption by the mother as well as heat dissipation due to conductive and convective exchange would offer significant protection. However, a theoretical 1-W/kg exposure averaged over the entire 28-day embryo, or averaged over a 1-g volume in the foetus, should not elevate temperature more than 0.2°C. Because of safety standards, exposures to the foetus this great would not be attainable with the usual RF sources. Foetal exposures to ultrasound are limited by the US Food and Drug Administration (FDA) to a maximum spatial peak temporal average intensity of 720?mW/cm². Routine ultrasound scanning typically occurs at lower values and temperature elevations are negligible. However, some higher power Doppler ultrasound devices under some conditions are capable of raising foetal temperature several degrees and their use in examinations of the foetus should be minimised.     

Bleomycin, vincristine, lomustine, and DTIC chemotherapy for metastatic melanoma

Forty-six consecutive, evaluable patients with a diagnosis of metastatic melanoma without prior chemotherapy were treated with bleomycin, vincristine, lomustine, and DTIC (BOLD). Treatment was repeated every 28 days for two cycles. Complete restaging then was performed, and response to treatment was determined. Of the 46 patients, five (11%) achieved a complete response, five (11%) achieved a partial response, nine (19%) obtained disease stabilization, and 27 (59%) had progressive disease. If four patients who died of rapidly progressive disease are included, the response rate drops to 20%. Overall median survival was 6 months. These results are inferior to the 40% and 46% response rates reported by other investigators. The modest response rate toxicity and expense of the regimen do not support its use in metastatic melanoma except, perhaps, in selected patients with soft tissue and/or lung metastasis.     

Standards, options, and recommendations for radiotherapy of kidney cancer]

CONTEXT: The "Standards, Options and Recommendations" (SOR), initiated in 1993, is a collaborative project between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary expert group, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for the diagnosis, management and treatment of patients with renal cancer. This review is part of previously published complete guidelines and focuses on the place of radiotherapy in this disease. METHODS: The data was identified by literature search using Medline (up to June 1999) and personal reference lists. The main endpoints considered were survival, risk factors for late effects of radiotherapy, safety and quality of life. RESULTS: The key recommendations are: 1) In localised renal cancer, adjuvant radiotherapy has a limited role: it is not indicated for T1 and T2 tumours and there is no proof of a survival benefit for T3 N1-N2 tumours. Postoperative radiotherapy can be considered in young patients without risk factors for the development of post-radiotherapy complications and without loco-regional invasion (renal capsule, renal pelvis, vena cava, regional lymph nodes); 2) For metastatic tumours, the multidisciplinary team must decide whether palliative radiotherapy is appropriate after consideration of the prognostic factors. An isolated metastasis can be treated by radiosurgery and stereotaxic radiosurgery may be of benefit in the case of one or two cerebral metastasis. The optimal dose for palliative treatment is not known. Radiotherapy followed by immunotherapy can also be considered if the patient has no contraindication to such treatments.     

Cisplatin, vinblastine, and mitoguazone chemotherapy for epidermoid and adenocarcinoma of the esophagus

Thirty-six patients with adenocarcinoma or epidermoid carcinoma of the esophagus were entered into a phase II trial evaluating the combination of cisplatin 100 mg/m2 intravenously (IV) day 2, vinblastine 1.6 mg/m2 IV days 1 to 4, and mitoguazone (MGBG) 500 mg/m2 IV days 1 and 8. Twenty-nine patients (group A) were newly diagnosed with local-regional disease only and were candidates for transhiatal esophagectomy (THE). These patients received two courses of chemotherapy at 3-week intervals prior to surgery. Response was assessed by measuring changes in the primary tumor length and depth on serial biphasic contrast esophagrams and comparing this result with tumor measurements obtained from the surgical specimen. Complete (CR) and partial responders (PR) received three additional postoperative cycles. Seven patients had recurrent or metastatic disease (group B) and were treated every 4 weeks until disease progression. Of 34 patients evaluable for response, there was one pathologically confirmed CR and 15 PRs (47%). This consisted of 12 of 27 (44%) group A patients (seven of 11 epidermoid, five of 16 adenocarcinoma) and four of seven (57%) group B patients (two of four epidermoid, two of three adenocarcinoma). Toxicity included leukopenia in one third of treatment courses and thrombocytopenia in 21%. Nausea and vomiting occurred in 60% of patients, diarrhea in 18%, transient nephrotoxicity in 18%, peripheral neuropathy in 12%, and ototoxicity in 3%. Twenty-five group A patients underwent resection. Four chemotherapy nonresponders (NR) and one PR had known disease left at surgery; all others (80%) had gross total removal of their disease. The median survival time (MST) of the 29 group A patients was 14 months, with 21% alive at 36 months. The MST of group A chemotherapy responders was 15 months compared with 9 months for NRs (P = .032). Initial sites of recurrence in 14 patients were local-regional in six, distant only in six, both local-regional and distant in two. This regimen, administered in maximally tolerated doses, was active in epidermoid and adenocarcinoma histologies, recurrent disease and newly diagnosed patients. However, nearly all responses were PRs and the MST of resected patients was similar to a prior series of patients treated with esophagectomy alone. Observations from this pilot trial and those of others have led to a follow-up study, in progress, evaluating intensive preoperative chemotherapy and concurrent radiation therapy (RT).     

Efficacy of aprepitant for CHOP chemotherapy-induced nausea,vomiting, and anorexia

The objective of this study was to evaluate whether aprepitant in addition to 5-HT3 receptor antagonist is useful for preventing chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients receiving CHOP therapy, and to evaluate the relationship between in vivo kinetics of plasma substance P and these adverse events. Patients with malignant lymphoma who received CHOP chemotherapy or THP (THP-ADR)-COP therapy were investigated for CINV and anorexia for 5 days after the start of chemotherapy. With the first course of chemotherapy, all patients received only granisetron on day1 as an antiemetic. Patients who experienced nausea, vomiting, or anorexia exceeding grade 1 in the first course received aprepitant for 3 days in addition to granisetron with the second course of CHOP chemotherapy. Plasma substance P concentrations at 24 and 72 hours after chemotherapy were measured. Nineteen patients were evaluated. Nausea, vomiting, or anorexia was observed with the first course in 7 of 19 patients. During the second course with aprepitant, no patients experienced vomiting, and the toxicity grade of nausea, vomiting, or anorexia was decreased compared with those in the first course. Substance P concentrations showed no differences after chemotherapy, in patients with nausea, vomiting, or anorexia and in patients without. The addition of aprepitant to 5-HT3 receptor antagonist appears effective for CINV or anorexia for patients who received CHOP chemotherapy.     

Ecological study for refrigerator use, salt, vegetable, and fruit intakes, and gastric cancer

We used an ecological approach to determine the correlation between vegetable, fruit and salt intakes, refrigerator use, and gastric cancer mortality in Korean population. Information on fruit and vegetable intakes per capita from the National Health and Nutrition Survey, death certificate data from the National Statistical office, refrigerator per household data from Korean Statistical Information Service, and salt/sodium intake data from a cross-sectional survey were utilized. Correlation coefficients were calculated between vegetable and fruit intakes, refrigerator per household, and gastric cancer mortality and between salt and sodium intakes, and gastric cancer mortality and incidence in the four areas. With 5, 10, and 15?years lag time, refrigerator usage and fruit intake were negatively associated with gastric cancer mortality (p?相似文献