Treatment of unresectable or metastatic osteosarcoma with cisplatin or cisplatin-doxorubicin

Responses and toxicity after treatment with cisplatin and cisplatin-doxorubicin were compared in two groups of patients with unresectable or metastatic osteosarcoma. Complete or partial responses developed in 3 of 18 individuals treated with cisplatin, and in 5 of 19 after the two-drug combination. Hematologic and gastrointestinal complications were more frequent and severe in patients who received both agents. The combined use of cisplatin and doxorubicin is justified for patients with unresectable or metastatic osteosarcoma at diagnosis because of the potential therapeutic benefits for these individuals.     

Investigating Hardy-Weinberg equilibrium in case-control or cohort studies or meta-analysis

Yu et al. (Breast Cancer Res Treat 117:675–677, 2009) recently stated that testing for deviation from Hardy–Weinberg equilibrium (HWE) is necessary to identify systematic genotyping errors in case–control studies. They criticized a meta-analytic study for the deviation from HWE in the case group of one study. The aim of this article is twofold. First, we derive recommendations on how to test for deviations from HWE in different study designs. Second, we develop a meta-analytic framework for assessing compatibility with HWE or measuring deviation from HWE. The authors sketch the possible reasons behind deviation from HWE and provide guidelines for proper investigation of HWE deviations in different study designs. The authors argue that the standard HWE χ² lack of fit test is logically flawed and provide a logically unflawed approach for measuring deviation from HWE using confidence intervals. The proposed method is applicable to meta-analyses of both case–control or cohort association studies. The proposed approach is illustrated using the meta-analysis criticized by Yu et al. Heterogeneity between studies can be assessed. The critique of Yu et al. to the article of Frank et al. (Breast Cancer Res Treat 111:139–144, 2008) can be refuted. Even more, validity of HWE can be proven for the pooled control sample. The authors advocate the use of a confidence interval-based approach to assess HWE. The latter should only be investigated in control populations. In multicenter studies or meta-analysis, deviation from HWE should be analyzed using a meta-analytic approach.     

Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients

The aim of this study was to assess whether a combination of gemcitabine (GEM) with either paclitaxel (PTX) or vinorelbine (VNR) could be more effective than GEM or PTX alone in elderly or unfit advanced non-small-cell lung cancer (NSCLC) patients. A total of 264 NSCLC patients aged >70 years with ECOG performance status (PS)< or =2, or younger with PS=2, were randomly treated with: GEM 1200 mg m(-2) on days 1, 8 and 15 every 28 days; PTX 100 mg m(-2) on days 1, 8 and 15 every 28 days; GEM 1000 mg m(-2) plus PTX 80 mg m(-2) (GT) on days 1 and 8 every 21 days; GEM 1000 mg m(-2) plus VNR 25 mg m(-2) (GV) on days 1 and 8 every 21 days. In all arms, an intra-patients dose escalation was applied over the first three courses, provided that no toxicity of WHO grade > or =2 had previously occurred. At present time, 217 (82%) patients had died. The median (months) and 1-year survival probability were 5.1 and 29% for GEM, 6.4 and 25% for PTX, 9.2 and 44% for GT, and 9.7 and 32% for GV. Multivariate analysis showed that PS< or =1 (hazard ratio (HR)=0.67; 95% CI 0.51-0.90), and doublet treatments (HR=0.76; 95% CI 0.59-0.99) were significantly associated with longer survival. Doublets produced no more toxicity than single agents. GT should be considered a reference regimen for elderly NSCLC patients with PS< or =1.     

Gemcitabine alone or combined with cisplatin in relapsed or refractory multiple myeloma

Gemcitabine is a pyrimidine nucleoside analog with antitumor activity against solid tumor malignancies and leukemia. We evaluated its activity as a single agent and combining it with cisplatin in relapsed-refractory multiple myeloma (MM). Sixteen patients with advanced MM received intravenous gemcitabine 1250 mg/mq (days 1, 8 and 15) as a single agent for a total of 3 monthly courses. The responders received another three courses, and the non-responders received three courses of gemcitabine 1000 mg/mq (days 1, 8 and 15) plus cisplatin 80 mg/mq (day 1). No grade 4 hematological toxicity was seen after gemcitabine treatment, whereas > or = 3 grade neutropenia and thrombocytopenia were seen in 21 and 13% of the gemcitabine-cisplatin infusions, respectively. Non-hematological toxicity was negligible for both the regimens. After three courses of gemcitabine as a single agent, th e response rate was 31% (1 complete response, 1 partial response and 3 minimal response). Eight patients (50%) achieved stable disease and 3 (19%) had disease progression. Ten patients received gemcitabine-cisplatin and were evaluable for the response. Two patients progressed, four maintained stable disease whereas four patients, unresponsive to gemcitabine, obtained a response (3 partial response and 1 minimal response). With a median follow-up of 13 months (range 8-17.5), 7 patients (44%) died, 5 (31%) had disease progression, 1 (6%) relapsed, 1 was still in partial response (+11 months) and 2 (13%) had a stable disease. Median time to treatment failure (TTF) was 8 months (CI95%: 7.6-8.4) and median overall survival (OS) was 16 months (CI95%: 10-22). These results showed that gemcitabine and gemcitabine-cisplatin were feasible regimens and well tolerated in advanced relapsed-refractory MM. The response rates, the TTF and OS were similar to other salvage chemotherapy regimens; nevertheless, the quality of response was modest particularly after gemcitabine alone. Better results might be obtained combining gemcitabine with other chemotherapy compounds or with biologically based therapies.     

Outcomes in Patients With Relapsed or Refractory Acute Promyelocytic Leukemia Treated With or Without Autologous or Allogeneic Hematopoietic Stem Cell Transplantation

BackgroundOutcomes in patients with acute promyelocytic leukemia (APL) have improved; however, a significant number of patients still relapse despite receiving all-trans-retinoic acid (ATRA) and arsenic-based therapies.Patients and MethodsOutcomes of patients with relapsed APL who were treated at our institution (1980-2010) and who received HCT were compared with those who received chemotherapy (CT) only.ResultsAmong 40 patients, 24 received HCT (autologous [auto] HCT, 7; allogeneic [allo] HCT, 14; both, 3); 16 received CT only. The median age at diagnosis was 36 years (range, 13-50 years), 31 years (range, 16-58 years), and 44 years (range, 24-79 years) for the auto-HCT, allo-HCT, and CT groups, respectively. Ten (100%) patients who received auto-HCT and 12 (71%) who received allo-HCT were in complete remission at the time of the HCT. The median follow-ups in the auto-HCT, allo-HCT, and CT groups were 74 months (range, 26-135 months), 118 months (range, 28-284 months), and 122 months (range, 32-216 months), respectively. Transplantation-related mortality (1 year) after auto-HCT and allo-HCT were 10% and 29%, respectively. The 7-year event-free survival after auto-HCT and allo-HCT was 68.6% and 40.6%, respectively (P = .45). The 7-year overall survival was 85.7%, 49.4%, and 40% in the auto-HCT, allo-HCT, and CT groups, respectively (P = .48).ConclusionBoth auto-HCT and allo-HCT are associated with durable remission and prolonged survival. All 3 strategies (auto-HCT, allo-HCT, CT) were found to be feasible in the relapsed APL setting and result in long-term disease control in selected patients. In this retrospective analysis, overall survival for patients who received HCT was not significantly better than patients who received CT only, but a trend toward better outcomes was seen in patients who underwent auto-HCT, although not statistically significant.     

Complications following surgery with or without radiotherapy or radiotherapy alone for prostate cancer

Background:

Men undergoing treatment of clinically localised prostate cancer may experience a number of treatment-related complications, which affect their quality of life.

Methods:

On the basis of population-based retrospective cohort of men undergoing surgery, with or without subsequent radiotherapy, or radiotherapy alone for prostate cancer in Ontario, Canada, we measured the incidence of treatment-related complications using administrative and billing data.

Results:

Of 36 984 patients, 15 870 (42.9%) underwent surgery alone, 4519 (12.2%) underwent surgery followed by radiotherapy, and 16 595 (44.9%) underwent radiotherapy alone. For all end points except urologic procedures, the 5-year cumulative incidence rates were lowest in the surgery only group and highest in the radiotherapy only group. Intermediary rates were seen in the surgery followed by radiotherapy group, except for urologic procedures where rates were the highest in this group. Although age and comorbidity were important predictors, radiotherapy as the primary treatment modality was associated with higher rates for all complications (adjusted hazard ratios 1.6–4.7, P=0.002 to <0.0001).

Conclusions:

In patients treated for prostate cancer, radiation after surgery increases the rate of complications compared with surgery alone, though these rates remain lower than patients treated with radiation alone. This information may inform patient and physician decision making in the treatment of prostate cancer.     

Radiation therapy after breast augmentation or reconstruction in early or recurrent breast cancer

Fourteen patients whose augmented or reconstructed breasts were treated with radiation therapy were analyzed. Silicone gel implants were used in 13 patients and free-injected silicone in one patient. The total radiation dose ranged from 4400 to 6200 cGy using tangential photon fields or an en face electron field by megavoltage equipment. In several cases, electron boost radiation was added to the tumor bed. The majority of the patients tolerated therapy well with minimal transient skin reactions; only three patients required a treatment break secondary to moist desquamation. Three patients developed documented implant encapsulation, although the majority retained good to excellent cosmesis. In summary, when breast carcinoma arises in the augmented or reconstructed breast, conservative management (i.e., limited surgery and definitive irradiation) is feasible without compromising the therapy or the cosmetic result. Thus, conservative management should be offered as an option to patients who are interested in breast prosthesis conservation.     

Conditional immortalization and/or transformation of rat cells carrying v-abl or EJras oncogene in the presence or absence of glucocorticoid hormone

Early-passaged rat chondroblasts (RX cells) and embryonal fibroblasts (RE cells) are hardly transformed by transfection of activated human H-ras (EJras) or by Abelson murine leukemia virus v-abl oncogene. However, these cells were transformed by v-abl or EJras gene when dexamethasone (DX) was added in the culture medium as well as when co-transfected with retrovirus LTR-linked mouse c-myc gene. RX cell lines carrying v-abl (RXabl), RE cell lines carrying v-abl (REabl) and RX cell lines carrying EJras (RXEJ) were established from transformed colonies in the DX-added soft agar. In the absence and in the presence of DX, RXabl cells showed mortal and immortalized, REabl cells showed mortal and transformed, and RXEJ cells showed immortalized and transformed phenotypes, respectively. Especially, immortalization and transformation of REabl1 and REabl3 lines were switched on and off by addition and depletion of DX. v-abl or EJras mRNA levels in tested REabl, RXabl and RXEJ lines cultured without DX was not decreased compared to those cultured with the hormone. The above suggests that, like myc gene, glucocorticoid collaborates with v-abl or activated ras oncogene to transform unestablished rat cells and that the transformation phenotypes were determined not only by the introduced oncogene but by the cellular condition including their tissue origin. Transformation of senescent REabl cells in the absence of DX was tested by transfecting different oncogenes. Among nuclear oncogenes tested, only adenovirus 12 E1A gene could induce transformation of G0-arrested REabl cells in a cooperative fashion with the integrated v-abl gene.     

Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer: a randomized phase II study

BackgroundDocetaxel/cisplatin/infusional 5-fluorouracil (5-FU; DCF) is a standard chemotherapy regimen for patients with advanced gastric cancer (GC). This phase II study evaluated docetaxel/oxaliplatin (TE), docetaxel/oxaliplatin/5-FU (TEF), and docetaxel/oxaliplatin/capecitabine (TEX) in patients with advanced GC.Patients and methodsPatients with metastatic or locally recurrent gastric adenocarcinoma (including carcinoma of the gastro-oesophageal junction) were randomly assigned (1 : 1 : 1) to TE, TEF, or TEX. Each regimen was tested at two doses before full evaluation at optimized dose levels. The primary end point was progression-free survival (PFS). Overall survival (OS), tumour response, and safety were also assessed. A therapeutic index (median PFS relative to the incidence of febrile neutropenia) was calculated for each regimen and compared with DCF (historical data).ResultsOverall, 248 patients were randomly assigned to receive optimized dose treatment. Median PFS was longer with TEF (7.66 [95% confidence interval (CI): 6.97–9.40] months) versus TE (4.50 [3.68–5.32] months) and TEX (5.55 [4.30–6.37] months). Median OS was 14.59 (95% CI: 11.70–21.78) months for TEF versus 8.97 (7.79–10.87) months for TE and 11.30 (8.08–14.03) months for TEX. The rate of tumour response (complete or partial) was 46.6% (95% CI 35.9–57.5) for TEF versus 23.1% (14.3–34.0) for TE and 25.6% (16.6–36.4) for TEX. The frequency and type of adverse events (AEs) were similar across the three arms. Common grade 3/4 AEs were fatigue (21%), sensory neuropathy (14%), and diarrhoea (13%). Febrile neutropenia was reported in 2% (TEF), 14% (TE), and 9% (TEX) of patients. The therapeutic index was improved with TEF versus TEX, TE, or DCF.ConclusionThese results suggest that TEF is worthy of evaluation as an arm in a phase III trial or as a backbone regimen for new targeted agents in advanced GC.ClinicalTrials.gov IdentifierTrial registration number: NCT00382720.     

Intrapleural or Intraperitoneal Lobaplatin for Treatment of Patients with Malignant Pleural Effusion or Ascites

Aims: To explore efficacy and side effects of intrapleural or intraperitoneal lobaplatin for treating patientswith malignant pleural or peritoneal effusions. Methods: Patients in Jiangsu Cancer Hospital and ResearchInstitute with cytologically confirmed solid tumors complicated with malignant pleural effusion or ascites wereenrolled into this study. Lobaplatin (20-30 mg/m2) was intrapleurally or intraperitoneally infused for patientswith malignant pleural effusion or ascites. Results: From 2012 to 2013, intrapleural or intraperitonea lobaplatinwas administered for patients with colorectal or uterus cancer who were previous treated for malignant pleuraleffusion or ascites. Partial response was achieved for them. Main side effects were nausea/vomiting, and bonemarrow suppression. No treatment related deaths occurred. Conclusion: Intrapleural or intraperitoneal infusionof lobaplatin is a safe treatment for patients with malignant pleural effusion or ascites, and the treatment efficacyis encouraging.