Anti-VEGF Therapy with Bevacizumab - Limited Cardiovascular Toxicity

Purpose: This analysis was conducted to evaluate cardiovascular toxicity of commonly used anti-VEGFtherapeutic agent, bevacizumab, in treating patients with cancer. Methods: Clinical studies evaluating the efficacyand safety of bevacizumab-based regimens on response and safety for patients with cancer were identified usinga predefined search strategy, allowing cardiovascular toxicity and other side effects of treatment to be estimated.Results: In bevacizumab based regimens, 4 clinical studies including 282 patients with advanced cancer (includinggliomas, cervical, breast and ovarian cancer) were considered eligible for inclusion. These bevacizumab-basedregimens included docetaxel, irinitecan and carboplatin. Systematic analysis suggested that, of 282 patientstreated by bevacizumab based regimens, hypertension and thrombo-embolism occurred in 2.5% (7/282), whileonly 3 patients reported cardiovascular events (1.1%). No treatment related death occurred in bevacizumabbased treatment.Conclusion: This systemic analysis suggests that bevacizumab based regimens are associatedwith reasonable and accepted cardiovascular toxicity when treating patients with gliomas, cervical, breast andovarian cancer.     

成核透明剂ZC-3的急性毒性和遗传毒性试验

背景与目的:研究成核透明剂ZC-3(DMDBS)的急性毒性和遗传毒性.材料与方法:小鼠急性毒性试验、Ames试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验.结果:急性毒性试验表明:成核透明剂ZC-3属无毒物质.Ames试验、微核试验和精子畸形试验结果均为阴性.结论:在本次实验条件下,成核透明剂ZC-3为无毒物质,未显示有遗传毒性作用.     

Toxicity from chemoradiotherapy in older patients with glioblastoma multiforme

Objectives The optimal treatment for elderly patients (age > 70 years) with glioblastoma remains controversial. We conducted a prospective trial in 32 consecutive elderly patients with glioblastoma who underwent surgery followed by radiotherapy (RT) plus concomitant and adjuvant temozolomide. Patients and Methods 32 patients 70 years of age or older with a newly diagnosed glioblastoma and a Karnofsky performance status (KPS) ≥ 70 were treated with RT (daily fractions of 2 Gy for a total of 60 Gy) plus temozolomide at the dose of 75 mg/m² per day followed by six cycles of adjuvant temozolomide (150–200 mg/m² for 5 days during each 28-day cycle). The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS) and toxicity. Results The median OS was 10.6 months and the median PFS was 7 months. The 6-month and 12-month survival rates were 91% and 37%, respectively. The 6-month and 12-month PFS rates were 56% and 16%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (P = 0.01). Adverse effects were mainly represented by neurotoxicity (40%), which resolved in most cases with the use of steroids, and Grade 3–4 hematologic toxicity in 28% of patients. Chemotherapy was stopped in 2 patients, delayed in 9 patients and reduced in 4 patients. Conclusions Standard RT plus concomitant and adjuvant temozolomide is a feasible treatment for elderly patients with newly diagnosed glioblastoma who present with good prognostic factors.     

Toxicity of radiotherapy in patients with collagen vascular disease

BACKGROUND: A diagnosis of collagen vascular disease (CVD) may predispose to radiotherapy (RT) toxicity. The objective of the current study was to identify factors that influence RT toxicity in the setting of CVD. METHODS: A total of 86 RT courses for 73 patients with CVD were delivered between 1985 and 2005. CVD subtypes include rheumatoid arthritis (RA; 33 patients), systemic lupus erythematosus (SLE; 13 patients), scleroderma (9 patients), dermatomyositis/polymyositis (5 patients), ankylosing spondylitis (4 patients), polymyalgia rheumatica/temporal arteritis (4 patients), Wegener granulomatosis (3 patients), and mixed connective tissue disorders (MCTD)/other (2 patients). Each patient with CVD was matched to 1 to 3 controls with respect to sex, race, site irradiated, RT dose (+/-2 Gray), and age (+/-5 years). RESULTS: There was no significant difference between CVD patients (65.1%) and controls (72.5%) experiencing any acute toxicity. CVD patients had a higher incidence of any late toxicity (29.1% vs 14%; P = .001), and a trend toward an increased rate of severe late toxicity (9.3% vs 3.7%; P = .079). RT delivered to the breast had increased risk of severe acute toxicity, whereas RT to the pelvis had increased risk of severe acute and late toxicity. RT administered in the setting of scleroderma carried a higher risk of severe late toxicity, whereas RT to SLE patients carried a higher risk of severe acute and late toxicity. CONCLUSIONS: Although generally well tolerated, RT in the setting of CVD appears to carry a higher risk of late toxicity. RT to the pelvis or in the setting of SLE or scleroderma may predispose to an even greater risk of severe toxicity. These issues should be considered when deciding whether to offer RT for these patients.     

Toxicity of glutaminase in patients with advanced lymphoblastic leukaemia

Fifteen patients with relapsed lymphoblastic leukaemia were treated with a glutaminase isolated from Achromobacter sp. using this enzyme for the first time in combination with other drugs in the treatment of human leukaemia.Although two patients achieved complete remission, and a further three partial remission, five patients showed acute hypersensitivity to the glutaminase and two of the five required resuscitation. Also one patient developed hyperglycaemic ketoacidosis 36 h after receiving the enzyme for the first time, and three others had biochemical evidence of carbohydrate intolerance. All patients experienced nausea and vomiting shortly after the start of the first infusion which lessened with second and third courses, and did not necessitate withdrawal of the drug.The high incidence of side effects in these patients indicates that despite the anti-leukaemic activity of this enzyme its application is limited by poor patient acceptability.     

Cetuximab-Associated Pulmonary Toxicity

There is increasing evidence for the use of epidermal growth factor receptor (EGFR) inhibitors in head and neck, non–small-cell lung, and colorectal cancers. We report the case of a 78-year-old man with metastatic colorectal cancer (CRC) involving liver and lung who received cetuximab plus irinotecan as third-line treatment. Two months later, he presented with signs and symptoms consistent with bronchiolotis obliterans organizing pneumonia secondary to cetuximab. Reports of cetuximab-associated pulmonary toxicity are rare, although there have been extensive reports of interstitial fibrosis with the use of other EGFR inhibitors such as gefitinib and erlotinib. There are many causes of pulmonary infiltrates in patients treated for advanced CRC, and this case highlights the importance of considering drug toxicity.     

Oxaliplatin-Related Ocular Toxicity

We report the case of a 52-year-old woman with advanced colorectal cancer who was treated with oxaliplatin on a FOLFOX schedule. After 3 cycles of chemotherapy, she started to complain of visual loss, altered color vision and neurological symptoms. Due to the suspicion of ocular and neurological toxicity, antineoplastic treatment was stopped. Her visual field showed a concentric bilateral scotoma and the electrooculogram test revealed severe impairment of the retinal pigment epithelium. Visual acuity, color vision and visual field recovered completely 8 months later, although electrooculogram remained abnormal. Ocular toxicity has been reported as an infrequent adverse event of oxaliplatin. Findings in this case indicate toxicity of this chemotherapeutic agent on the retinal pigment epithelium, which has not been reported before. This damage could be permanent, and it thus differs from previously described oxaliplatin-induced ocular toxicities, which are usually transient and reversible. With increasing use of oxaliplatin as first-line treatment in advanced colorectal cancer, we have to be aware of this possible toxicity.     

Sex- and Age-Related Chemotherapy Toxicity in Patients with Non-Metastatic Osteosarcoma

Abstract

The influence of age and sex on chemotherapy-related toxicity was evaluated in children and adults with non metastatic osteosarcoma. Treatment consisted of methotrexate (MTX, 12 g/m²), cisplatin (CDP 120 mg/m²) and doxorubicin (ADM 75-90 mg/m²) and high-dose ifosfamide (HDIFO). Toxicity data from 1,051 courses (295 with MTX, 756 based on doxorubicin, cisplatin and high-dose ifosfamide) were analyzed. Children (4-14 yrs) and females showed a higher incidence of grade 4 neutropenia and thrombocytopenia and were more frequently hospitalized for neutropenic fever compared to adolescents and young adults (AYA, 15-19 yrs) and adults (>20-40 yrs). Delayed MTX excretion was higher in adults than AYA and children. Adults (up to 40 years) can be treated with pediatric protocols for osteosarcoma and they experience lower hematologic toxicity compared to pediatric population. Further investigations on sex-related susceptibility to chemotherapy in osteosarcoma patients are recommended.     

Toxicity after reirradiation of pulmonary tumours with stereotactic body radiotherapy

Purpose

To assess toxicity and feasibility of reirradiation with stereotactic body radiotherapy (SBRT) after prior lung SBRT for primary lung cancer or lung metastases.

Patients and materials

Twenty-nine patients reirradiated with SBRT on 32 lung lesions (11 central, 21 peripheral) were retrospectively reviewed. Median follow-up time was 12 months (range 1-97). The primary endpoint was toxicity, secondary endpoints were local control and overall survival time. Toxicity was scored according to the NCI-CTCAE version 3.

Results

Grade 3-4 toxicity was scored 14 times in eight patients. Three patients died because of massive bleeding (grade 5). Larger clinical target volumes (CTV) and central tumour localization were associated with more severe toxicity. There was no correlation between mean lung dose (MLD) and lung toxicity. Local control at 5 months after reirradiation was 52%, as assessed by CT-scan (n = 12) or X-thorax (n = 3). A larger CTV was associated with poorer local control. Kaplan-Meier estimated 1- and 2-year survival rates were 59% and 43%, respectively.

Conclusions

Reirradiation with SBRT is feasible although increased risk of toxicity was reported in centrally located tumours. Further research is warranted for more accurate selection of patients suitable for reirradiation with SBRT.     

前列腺癌大分割调强放疗副反应初步分析

Objective To analyze the acute and late toxicities in patients with prostate cancer trea-ted with hypofractionated intensity-modulated radiotherapy (IMRT). Methods Between June 2006 and June 2008, 37 patients with prostate cancer were treated with hypofractionated IMRT. The clinical target vol-ume (CTV) was the prostate, seminal vesicles and pelvic lymph nodes in 24 patients, the prostate and semi-hal vesicles in 12, and only the tumor bed in 1. The dose per fraction was 2.3 - 2.8 Gy, with 2.7 Gy in 26 patients. The minimal dose was 62.5-75.0 Gy to the prostate and seminal vesicles, and 50 Gy to the pelvic lymph nodes. Results The median follow-up was 14 months. None of the patients experienced grade 4 a-cute gastro-intestinal (GI) toxicity. Grade 1, 2 and 3 acute GI toxicity occurred in 24.3%, 35.1% and 2.7% of the patients, respectively. The rectal V50>27% and V55>20% were highly significantly associat-ed with grade ≥1 acute GI toxicity. Grade 1,2 and 3 acute genitourinary (GU) toxicity occurred in 68%, 0% and 3% of the patients, respectively. The bladder V50> 10% was significantly associated with grade ≥1 acute GU toxicity. The incidence of late GI toxicity was low. No grade ≥3 late GI toxicity was observed. The incidence of late grade 1 and 2 GI toxicity was 24% and 5%, respectively. The rectal V65> 10% was highly significantly associated with grade ≥1 late GI toxicity. No late grade 4 GU toxicity was observed. The incidence of grade 1, 2 and 3 late GU toxicity was 49%, 11% and 3%, respectively. Grade ≥2 late GU toxicity was correlated with V40, V50 and mean dose of the bladder. Conclusions Acute and late toxicity of hypofractionated IMRT is acceptable in patients with prostate cancer.     

前列腺癌大分割调强放疗副反应初步分析

Objective To analyze the acute and late toxicities in patients with prostate cancer trea-ted with hypofractionated intensity-modulated radiotherapy (IMRT). Methods Between June 2006 and June 2008, 37 patients with prostate cancer were treated with hypofractionated IMRT. The clinical target vol-ume (CTV) was the prostate, seminal vesicles and pelvic lymph nodes in 24 patients, the prostate and semi-hal vesicles in 12, and only the tumor bed in 1. The dose per fraction was 2.3 - 2.8 Gy, with 2.7 Gy in 26 patients. The minimal dose was 62.5-75.0 Gy to the prostate and seminal vesicles, and 50 Gy to the pelvic lymph nodes. Results The median follow-up was 14 months. None of the patients experienced grade 4 a-cute gastro-intestinal (GI) toxicity. Grade 1, 2 and 3 acute GI toxicity occurred in 24.3%, 35.1% and 2.7% of the patients, respectively. The rectal V50>27% and V55>20% were highly significantly associat-ed with grade ≥1 acute GI toxicity. Grade 1,2 and 3 acute genitourinary (GU) toxicity occurred in 68%, 0% and 3% of the patients, respectively. The bladder V50> 10% was significantly associated with grade ≥1 acute GU toxicity. The incidence of late GI toxicity was low. No grade ≥3 late GI toxicity was observed. The incidence of late grade 1 and 2 GI toxicity was 24% and 5%, respectively. The rectal V65> 10% was highly significantly associated with grade ≥1 late GI toxicity. No late grade 4 GU toxicity was observed. The incidence of grade 1, 2 and 3 late GU toxicity was 49%, 11% and 3%, respectively. Grade ≥2 late GU toxicity was correlated with V40, V50 and mean dose of the bladder. Conclusions Acute and late toxicity of hypofractionated IMRT is acceptable in patients with prostate cancer.     

前列腺癌大分割调强放疗副反应初步分析

Objective To analyze the acute and late toxicities in patients with prostate cancer trea-ted with hypofractionated intensity-modulated radiotherapy (IMRT). Methods Between June 2006 and June 2008, 37 patients with prostate cancer were treated with hypofractionated IMRT. The clinical target vol-ume (CTV) was the prostate, seminal vesicles and pelvic lymph nodes in 24 patients, the prostate and semi-hal vesicles in 12, and only the tumor bed in 1. The dose per fraction was 2.3 - 2.8 Gy, with 2.7 Gy in 26 patients. The minimal dose was 62.5-75.0 Gy to the prostate and seminal vesicles, and 50 Gy to the pelvic lymph nodes. Results The median follow-up was 14 months. None of the patients experienced grade 4 a-cute gastro-intestinal (GI) toxicity. Grade 1, 2 and 3 acute GI toxicity occurred in 24.3%, 35.1% and 2.7% of the patients, respectively. The rectal V50>27% and V55>20% were highly significantly associat-ed with grade ≥1 acute GI toxicity. Grade 1,2 and 3 acute genitourinary (GU) toxicity occurred in 68%, 0% and 3% of the patients, respectively. The bladder V50> 10% was significantly associated with grade ≥1 acute GU toxicity. The incidence of late GI toxicity was low. No grade ≥3 late GI toxicity was observed. The incidence of late grade 1 and 2 GI toxicity was 24% and 5%, respectively. The rectal V65> 10% was highly significantly associated with grade ≥1 late GI toxicity. No late grade 4 GU toxicity was observed. The incidence of grade 1, 2 and 3 late GU toxicity was 49%, 11% and 3%, respectively. Grade ≥2 late GU toxicity was correlated with V40, V50 and mean dose of the bladder. Conclusions Acute and late toxicity of hypofractionated IMRT is acceptable in patients with prostate cancer.