john
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Teetlee,
Here is some research info. It happens to come from New Orleans
Glad you enjoyed your visit with the grandchild. Wishing you many more visits
Effective treatment of H838 human non-small cell lung carcinoma with a targeted cytotoxic somatostatin analog, AN-238.
Szereday Z, Schally AV, Szepeshazi K, Bajo AM, Hebert F, Halmos G, Nagy A.
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA 70112-1262, USA.
The accumulation of radioactive somatostatin analog [111In]pentetreotide in non-small cell lung cancer (non-SCLC) during scintigraphy of patients provides a rationale for investigating the efficacy of somatostatin receptor-based chemotherapy in non-SCLC. Consequently, in this study, we evaluated the antitumor effects of cytotoxic somatostatin analog AN-238 on H838 human non-SCLC xenografted into nude mice in comparison with its cytotoxic radical, 2-pyrrolinodoxorubicin (AN-201). The expression of messenger RNA (mRNA) for human somatostatin receptor subtypes 2 (hsst2) and 5 (hsst5) in H838 cells, and tumors was also investigated using reverse-transcription polymerase chain reaction (RT-PCR). Somatostatin receptors on H838 tumors were characterized by ligand competition assay using radiolabeled somatostatin analog, RC-160. Three i.v. injections of AN-238 at 150 nmol/kg, given on days 1, 7 and 21, resulted in a significant (p<0.05) tumor growth inhibition, the final tumor volume being 60% smaller than in the controls. The tumor doubling time was also extended significantly (p<0.05) from 9.65+/-0.56 days in the controls to 17.52+/-3.3 days. Only one of 8 mice died due to toxicity. In contrast, cytotoxic radical AN-201 was ineffective and more toxic, killing 2 of 7 animals. mRNA for hsst2 was found in H838 xenografts, but not in H838 cells from which the xenografts originated. Interestingly, H838 cells grown in a special, serum-free medium did express mRNA for hsst2. mRNA for hsst5 was not found in any samples tested. Binding studies demonstrated the presence of high affinity (Kd = 7.3+/-1.2 nM) binding sites for RC-160 with a mean maximal binding capacity (Bmax) of 953.3+/-45.3 fmol/mg protein. AN-238 at 3.14+/-0.93 nM concentration displaced 50% of radiolabeled RC-160 binding to somatostatin receptors in H838 tumors. Our results indicate that patients with inoperable non-SCLC may benefit from chemotherapy targeted to somatostatin receptors based on AN-238.
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I posted this a few places ... but it seemed like it is a topic of interest
Lung Cancer. 2003 May;40(2):173-80. Related Articles, Links
Frequent overexpression of the c-kit protein in large cell neuroendocrine carcinoma of the lung.
Araki K, Ishii G, Yokose T, Nagai K, Funai K, Kodama K, Nishiwaki Y, Ochiai A.
Pathology Division, National Cancer Center Research Institute East, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Chiba, Japan
Overexpression of receptor-type tyrosine kinases in various cancers is associated with an aggressive tumor phenotype and poor outcome, but their expression had never been evaluated in large cell neuroendocrine carcinoma (LCNEC) of the lung. In the present study, we investigated the expression of three receptor tyrosine kinases, epidermal growth factor receptor (EGFR), c-erbB-2, and c-kit protein, by comparing surgically resected 40 LCNECs with other neuroendocrine (NE) lung tumors: 9 typical carcinoids (TCs), 5 atypical carcinoids (ACs), and 13 small cell lung carcinomas (SCLCs). None of the NE lung tumors showed expression of EFGR or c-erbB-2, but c-kit was overexpressed in 55% of the LCNEC tumor cells and 46% of the SCLC tumor cells. None of the clinicopathologic factors in either the LCNEC or SCLC patients correlated with c-kit overexpression. The finding that c-kit expression in LCNEC is similar to its expression in SCLC suggests that inhibition of c-kit may be effective as a therapy targeting LCNEC as well as SCLC.
PMID: 12711118 [PubMed - in process]
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SCLC seems to express the c-kit gene. Gleevec may be an option. Someone on this website mentioned this before -
Lung Cancer. 2003 May;40(2):173-80. Related Articles, Links
Frequent overexpression of the c-kit protein in large cell neuroendocrine carcinoma of the lung.
Araki K, Ishii G, Yokose T, Nagai K, Funai K, Kodama K, Nishiwaki Y, Ochiai A.
Pathology Division, National Cancer Center Research Institute East, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Chiba, Japan
Overexpression of receptor-type tyrosine kinases in various cancers is associated with an aggressive tumor phenotype and poor outcome, but their expression had never been evaluated in large cell neuroendocrine carcinoma (LCNEC) of the lung. In the present study, we investigated the expression of three receptor tyrosine kinases, epidermal growth factor receptor (EGFR), c-erbB-2, and c-kit protein, by comparing surgically resected 40 LCNECs with other neuroendocrine (NE) lung tumors: 9 typical carcinoids (TCs), 5 atypical carcinoids (ACs), and 13 small cell lung carcinomas (SCLCs). None of the NE lung tumors showed expression of EFGR or c-erbB-2, but c-kit was overexpressed in 55% of the LCNEC tumor cells and 46% of the SCLC tumor cells. None of the clinicopathologic factors in either the LCNEC or SCLC patients correlated with c-kit overexpression. The finding that c-kit expression in LCNEC is similar to its expression in SCLC suggests that inhibition of c-kit may be effective as a therapy targeting LCNEC as well as SCLC.
PMID: 12711118 [PubMed - in process]
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Carleen - praying that everything works out with your husbands current treatment, but this may be something to look into if the response to his current treatment isnt up to your expectations.
gleevec targets the c-kit gene as other people have mentioned on here.
Lung Cancer. 2003 May;40(2):173-80. Related Articles, Links
Frequent overexpression of the c-kit protein in large cell neuroendocrine carcinoma of the lung.
Araki K, Ishii G, Yokose T, Nagai K, Funai K, Kodama K, Nishiwaki Y, Ochiai A.
Pathology Division, National Cancer Center Research Institute East, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Chiba, Japan
Overexpression of receptor-type tyrosine kinases in various cancers is associated with an aggressive tumor phenotype and poor outcome, but their expression had never been evaluated in large cell neuroendocrine carcinoma (LCNEC) of the lung. In the present study, we investigated the expression of three receptor tyrosine kinases, epidermal growth factor receptor (EGFR), c-erbB-2, and c-kit protein, by comparing surgically resected 40 LCNECs with other neuroendocrine (NE) lung tumors: 9 typical carcinoids (TCs), 5 atypical carcinoids (ACs), and 13 small cell lung carcinomas (SCLCs). None of the NE lung tumors showed expression of EFGR or c-erbB-2, but c-kit was overexpressed in 55% of the LCNEC tumor cells and 46% of the SCLC tumor cells. None of the clinicopathologic factors in either the LCNEC or SCLC patients correlated with c-kit overexpression. The finding that c-kit expression in LCNEC is similar to its expression in SCLC suggests that inhibition of c-kit may be effective as a therapy targeting LCNEC as well as SCLC.
PMID: 12711118 [PubMed - in process]
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Ray,
Sorry to hear the news, but it does not sound too bad. It sounds like your onc is hopeful and willing to work with you which is obviously good. Is there a chance at all for surgery and chemo? Below is an article saying that surgery is an option sometimes.
Lung cancer. Special treatment issues.
Detterbeck FC, Jones DR, Kernstine KH, Naunheim KS; American College of Physicians.
Multidisciplinary Thoracic Oncology Program, Division of Cardiothoracic Surgery, University of North Carolina, CB #7605, 108 Burnett-Womack Building, Chapel Hill, NC 27599-7065, USA. fdetter@med.unc.edu
This chapter of the Lung Cancer Guidelines addresses patients with particular forms of non-small cell lung cancer that require special considerations. This includes patients with Pancoast tumors, T4N0,1M0 tumors, satellite nodules in the same lobe, synchronous and metachronous multiple primary lung cancers (MPLC), and solitary metastases. For patients with a Pancoast tumor, a multimodality approach, involving chemoradiotherapy and surgical resection, appears optimal provided appropriate staging has been carried out. Patients with central T4 tumors that do not have mediastinal node involvement are uncommon. When carefully staged and selected, however, such patients appear to benefit from resection as part of the treatment as opposed to chemoradiotherapy alone. Patients with a satellite lesion in the same lobe as the primary tumor have a good prognosis and require no modification of the approach to evaluation and treatment from what would be dictated by the primary tumor alone. On the other hand, it is difficult to know how best to treat patients with a focus of the same type of cancer in a different lobe. Although MPLC do occur, the survival results after resection for either a synchronous presentation or a metachronous presentation with an interval of < 4 years between tumors are variable and generally poor, suggesting that many of these patients may have had a pulmonary metastasis rather than a second primary lung cancer. A thorough and careful evaluation of these patients is warranted to try to differentiate between patients with a metastasis and those with a second primary lung cancer, although criteria to distinguish them have not been defined. Finally, some patients with a solitary focus of metastatic disease in the brain or adrenal gland appear to benefit substantially from resection.
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Some research on antioxidants and chemo
The use of antioxidant therapies during chemotherapy.
Drisko JA, Chapman J, Hunter VJ.
Department of Obstetrics and Gynecology, School of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA. jdrisko@kumc.edu
OBJECTIVE: At the present time, many cancer patients combine some form of complementary and alternative medicine therapies with their conventional therapies. The most common choice of these therapies is the use of antioxidants. RESULTS: A review of four common antioxidants is undertaken, which includes vitamin E (mixed tocopherols and tocotrienols), beta-carotene (natural mixed carotenoids), vitamin C (ascorbic acid), and vitamin A (retinoic acid). Antioxidants act as electron acceptors as well as therapeutic biologic response modifiers. Despite the fact that chemotherapy-induced formation of free radicals is well-demonstrated, chemotherapy-induced cytotoxicity in general does not seem to depend on formation of reactive oxygen species. CONCLUSIONS: Currently, evidence is growing that antioxidants may provide some benefit when combined with certain types of chemotherapy. Because of the potential for positive benefits, a randomized controlled trial evaluating the safety and efficacy of adding antioxidants to chemotherapy in newly diagnosed ovarian cancer is underway at the University of Kansas Medical Center.
Publication Types:
Review
Review, Tutorial
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What did the doctor say about that SUV level?
I'm not a Dr but this is what I found on the net. generally, SUV > 3 are malignant. So 1.5 *probably* isnt bad. Talk to the Dr. I dont know if the sequential pet scans after waiting a period of time. That way there is a baseline and they can compare the different scans.
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The role of semiquantitative analysis for lesion characterization is limited, since there is an overlap of SUVs between benign and malignant lesions. Avril, using receiver operator characteristics (ROC) analysis and partial volume correction, found that an SUV of 2.5 offered the best diagnostic criterion.3 In general, lesions with an SUV greater than 3 are malignant. It should be noted that most studies of primary breast cancer have been performed with full-ring PET scanners. With such devices, sensitivity for lesions smaller than 1 cm has been suboptimal.
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US auditors criticize NIH for poor deal over Taxol royalties, while patent row continues in Canada | By Peg Brickley
US auditors released a study on Friday (June 6), criticizing the deal the National Institutes of Health (NIH) struck with drug giant Bristol-Myers Squibb to get the anticancer drug Taxol to market quickly.
The report by the General Accounting Office (GAO) said NIH's pact with Bristol-Myers Squibb (BMS) recovered only $35 million in royalty payments for Taxol after taxpayers spent $484 million to develop the best selling cancer drug in history.
Further, federal auditors said NIH failed to get adequate proof that BMS would sell Taxol at a reasonable price before handing over exclusive rights to make and market the drug developed by government-funded research. The company's sales revenue from Taxol was $9 billion between 1993 and 2002.
In a response, NIH said the auditors failed to recognize all the public benefits derived from NIH funding of the basic science behind paclitaxel, the active compound in Taxol. The GAO failed, for example, to include in its computations the $400 million in royalties Florida State University collected for a method to manufacture Taxol, the NIH response said.
"Our company met or exceeded every responsibility under the agreement [with NIH]," BMS spokesman Robert Hutchison said, commenting on the GAO report. "We are proud of our history with Taxol."
GAO's critique of the bargain NIH struck comes in the wake of settlements ending litigation that pitted all 50 states, five territories, and the District of Columbia, as well as hospitals and insurance companies, against BMS over the high price of Taxol. Those suits and an action by the Federal Trade Commission (FTC) accused the company of abusing the legal process to prolong its profitable monopoly on Taxol sales in the United States.
When NIH struck its deal with BMS in 1991, neither the federal agency nor anyone else knew the company planned to pursue patents on Taxol, said Meredyth Andrus, assistant attorney general in Maryland and one of the lead attorneys in the case against the drug maker.
"The negotiations with NIH were based on the fact that generics were going to come on the market once the 5-year period of exclusivity was over, so Bristol-Myers needed a price that would enable them to recover their marketing and manufacturing costs," Andrus said. "Everybody expected that would happen."
It did not happen because BMS was able to use its allegedly baseless patents to keep generics out of the market for years.
The GAO's report comes out as Canadian lawmakers wrestle over a regulatory scheme that seems to have handed BMS a chance to replay a similar scenario north of the border—one in which it gets a monopoly on Taxol and puts a tiny Canadian competitor with a low-priced alternative out of business.
BMS admitted no wrongdoing in the series of US Taxol settlements, including a recent one in which it agreed to return $135 million to the states, hospitals, and insurance companies who claim they were bilked on the price of Taxol. In April, the company came to terms with the FTC and agreed to refrain from asserting Taxol-related patents against generic rivals as part of a deal to end accusations that it had pursued baseless patents on the drugs after promising the NIH it would not and that it had used the patents to keep others out of the market.
But BMS is using patents it took out on Taxol in Canada against Biolyse Pharma, which wants to offer its naturally derived paclitaxel to cancer sufferers. The US drug giant won court victories against Biolyse that have kept the rival out of the market for years. In Canada, as in the United States, patent holders can invoke special protections to hold generic drug makers at bay for years.
"It's the same story, Canadian version," said Biolyse President Brigitte Kiecken. "Except it's worse in this scenario because we did our own research—15 years of research on this product." Biolyse scientists ran their own clinical trials and created a drug that is not simply a generic version of Taxol, she said. "Health Canada from the start always considered our product a novelty and a new drug," Kiecken said. "It's manufactured from a different species, and they said we can't assume it's the same; we have to show safety and efficacy through separate clinical trials."
Biolyse is prepared to sell its natural paclitaxel at a price that is less than one third of the price BMS is charging in Canada, she added.
June 2–4 saw a series of hearings in the House of Commons Industry Committee in which critics pointed to BMS's grip on the Taxol market as evidence of flaws in the Canadian patent system. "What it comes down to is that Bristol is dictating to our health authorities who gets what cancer treatment and at what price," Kiecken said.
BMS declined to comment on the Canadian dispute.
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This is only one study, but it seems good. And it was statistically significant
http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy.
Pace A, Savarese A, Picardo M, Maresca V, Pacetti U, Del Monte G, Biroccio A, Leonetti C, Jandolo B, Cognetti F, Bove L.
Neuroscience Department, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy. pace@ifo.it
PURPOSE: The aim of this study is to evaluate the neuroprotective effect of antioxidant supplementation with vitamin E in patients treated with cisplatin chemotherapy. METHODS: Between April 1999 and October 2000, forty-seven patients were randomly assigned to either group one, which received vitamin E supplementation during cisplatin chemotherapy, or to group two, which received cisplatin chemotherapy alone. Alpha-tocopherol (vitamin E; 300 mg/d) was administered orally before cisplatin chemotherapy and continued for 3 months after the suspension of treatment. For preclinical studies, nude mice carrying the human melanoma tumor were treated with cisplatin alone or in combination with vitamin E. RESULTS: Twenty-seven patients completed six cycles of cisplatin chemotherapy: 13 patients in group one and 14 patients in group two. The incidence of neurotoxicity was significantly lower in group one (30.7%) than it was in group two (85.7%; P <.01). The severity of neurotoxicity, measured with a comprehensive neurotoxicity score based on clinical and neurophysiological parameters, was significantly lower in patients who were supplemented with vitamin E than in patients who were not supplemented with vitamin E (2 v 4.7, P <.01). The results of the preclinical studies showed that when cisplatin was combined with vitamin E, no differences were observed in tumor weight inhibition, tumor growth delay, or life span as compared with treatment with cisplatin alone. CONCLUSION: Supplementation of patients receiving cisplatin chemotherapy with vitamin E decreases the incidence and severity of peripheral neurotoxicity.
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Whey protein contains a bunch of amino-acids - This info seems to contradict the benefits of whey protien I have read elsewhere
Very confusing
Phenylalanine can promote the cell division of existing malignant melanoma cells. If you have melanoma, or any other form of cancer for that matter, avoid phenylalanine. According to a study in the Journal of Human Nutrition and Dietetics, three patients with metastatic melanoma and three with metastatic breast cancer took part in a study that involved a diet of phenylalanine and tyrosine administered at a very low dose (10 mg/kg/day for 1 month). The results were not good. Researchers reported that all the patients experienced anxiety and depression and other side effects. They also lost weight. The authors of this pilot study concluded: "Low phenylalanine and tyrosine diets do not appear to be a viable treatment option for patients with advanced cancer" (Harvie et al. 2002).
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Interesting article at nature.com
"....
Most tumours have a dense extracellular matrix that inhibits drug diffusion and serves as a barrier to drug delivery. One of the key components of this barrier is a dense collagen meshwork, although the structure and content of the collagen networks varies between tumour types. Brown et al. have used a non-invasive imaging technique to quantify its density in vivo, allowing researchers to estimate the penetrability of tumours to molecular therapeutics.
Brown et al. used a principle called second harmonic generation (SHG) — an intrinsic fluorescent signal that can be detected without the addition of dyes or other reagents — to obtain high-resolution three-dimensional images of fibrillar collagen in vivo. SHG imaging allowed the authors to view and measure the density of fibrillar structures in different tumour types in mice (image shows SHG signal of collagen in red and cancer cell nuclei in green).
The SHG signal was found to vary among tumour types and was correlated with collagen content, as confirmed by other methods such as immunohistochemical staining of tissue sections. When the authors applied collagenase enzymes to mouse melanomas and imaged them in vivo, the SHG signal gradually faded, indicating the breakdown of the collagen matrix. Furthermore, as the SHG signal decreased, the diffusion co-efficient of a labelled molecular probe increased.
The hormone relaxin, which, among other functions, induces cells to produce matrix metalloproteinases (MMPs), also induced matrix changes that could be detected by SHG. SHG imaging showed that when mice were treated with relaxin, the average length and brightness of pre-existing fibres decreased significantly. Furthermore, the diffusion coefficients of fluorescent molecular probes increased, indicating a 'loosening' of the extracellular matrix. The authors concluded that the matrix of tumours in relaxin-treated mice had a more porous structure, leading to increased molecular mobility.
This simple and rapid technique could be used to determine the density of a tumour's collagen meshwork and estimate its potential for drug delivery, obviating the need for biopsies, tissue sectioning or staining. SHG has also provided insight into the mechanisms by which relaxin alters the tumour matrix, providing a new technology to evaluate alternative strategies for modifying the tumour extracellular matrix.
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From Drweil.com
Tip: Herb of the Week: Milk Thistle
Anyone who is a frequent user of alcohol should take milk thistle (Silybum marianum) regularly. This herb, from the tradition of European folk medicine, enhances the metabolism of liver cells and protects them from toxic injury. I also recommend this herb to my patients with chronic hepatitis, abnormal liver function, and those using pharmaceutical drugs that are hard on the liver (including cancer patients undergoing chemotherapy). You will find milk thistle products in all health-food stores. My preference is to use standardized extracts in tablet or capsule form. Follow the suggested dosage on the product you buy, or take two tablets or capsules twice a day. The herb is nontoxic and you can stay on it indefinitely.
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carboxyamido-triazole (CAI) is another anti-angiogenesis drug. There is a phase III - though it is double blind trial. I think it is in CA and recruiting
http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
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Peggy,
They are doing a lot of trials with Irinotecan(cpt-11, camptosar) and other chemo(gemcitabine, cisplatin and others) in Japan for NSCLC.
They can be found on pubmed
The response rate for CPT-11 and cisplatin in this study was 44%
Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer.
Negoro S, Masuda N, Takada Y, Sugiura T, Kudoh S, Katakami N, Ariyoshi Y, Ohashi Y, Niitani H, Fukuoka M; CPT-11 Lung Cancer Study Group West.
Department of Clinical Oncology, Osaka City General Hospital, Osaka, Japan. m6122765@msic.med.osaka-cu.ac.jp
To determine a standard combination chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC), we conducted a phase III trial of irinotecan (CPT-11) to test the hypotheses that CPT-11+cisplatin is superior to cisplatin+vindesine and that CPT-11 monotherapy is not inferior to cisplatin+vindesine. A total of 398 patients with previously untreated NSCLC were randomised to receive cisplatin+CPT-11 (CPT-P), cisplatin+vindesine (VDS-P) or CPT-11 alone (CPT). In the CPT-P arm, CPT-11 60 mg m(-2) was administered on days 1, 8 and 15, and cisplatin 80 mg m(-2) was administered on day 1. In the VDS-P arm, cisplatin 80 mg m(-2) was administered on day 1, and vindesine 3 mg m(-2) was administered on days 1, 8 and 15. In the CPT arm, CPT-11 100 mg m(-2) was administered on days 1, 8 and 15. The median survival time was 50.0 weeks for patients on CPT-P, 45.6 weeks for those on VDS-P and 46.0 weeks for those on CPT (P=0.115, CPT-P vs VDS-P; P=0.089, CPT vs VDS-P), and the hazard ratio was 0.85 (95% confidence interval (CI): 0.65-1.11) for CPT-P vs VDS-P and 0.83 (0.64-1.09) for CPT vs VDS-P. The response rate was 43.7% for patients on CPT-P, 31.7% for those on VDS-P and 20.5% for those on CPT. Major adverse reactions were grade 4 neutropenia observed in 37, 54 and 8% of the patients on CPT-P, VDS-P and CPT, respectively; and grades 3 and 4 diarrhoea observed in 12, 3 and 15% of the patients, respectively. CPT-P therapy produces comparable survival to VDS-P in patients with advanced NSCLC. CPT-11 monotherapy is not inferior to VDS-P in terms of survival. The CPT-11-containing regimen is one of the most efficacious and well tolerated in the treatment of advanced NSCLC.
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Prevention of bone metastases from breast cancer by adjuvant bisphosphonate therapy.
Kohno N, Kokufu I.
Department of Surgery, Hyogo Medical Center for Adults 13-70, Kitaoji-cho Akashi City, Hyogo 673-8558, Japan.
There is increasing evidence regarding the importance of osteoclast activation in the pathogenesis of bone metastases. Cancer cells produce osteoclast-activating factors which play an important role in the development of bone metastases. Bisphosphonates are drugs that inhibit bone turnover by decreasing bone resorption. In patients with bone metastases from breast cancer, the effectiveness of bisphosphonate is well established for reducing skeletal complications, such as bone pain, pathological fracture, bone surgery and hypercalcemia. Recent attention has focused on a possible preventive effect on bisphosphonates of bone metastases. Animal models have supported the prevention of bone metastasis by bishosphonate therapy, but three major adjuvant clinical trials of the oral bisphosphonate clodronate have yielded conflicting results. However, our preliminary trial of intravenous bisphosphonate with pamidronate showed effective inhibition of bone metastases. Use of bisphosphonates as adjuvant therapy is still investigational yet promising. Several more randomized trials are underway to further investigate adjuvant therapy with bisphosphonates
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It seems from this research that clodronate is NOT effective and actually may make things worse
http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract
Adjuvant clodronate treatment does not reduce the frequency of skeletal metastases in node-positive breast cancer patients: 5-year results of a randomized controlled trial.
Saarto T, Blomqvist C, Virkkunen P, Elomaa I.
Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
PURPOSE: Bisphosphonates have effectively reduced the development and progression of bone metastases in advanced breast cancer. The aim of this study was to determine whether bone metastases could be prevented by adjuvant clodronate treatment in patients with primary breast cancer. PATIENTS AND METHODS: Between 1990 and 1993, 299 women with primary node-positive breast cancer were randomized to clodronate (n = 149) or control groups (n = 150). Clodronate 1,600 mg daily was given orally for 3 years. All patients received adjuvant therapy: premenopausal six cycles of CMF chemotherapy and postmenopausal antiestrogens (randomized to tamoxifen 20 mg or toremifene 60 mg/d for 3 years). Seventeen patients were excluded from the analyses because of major protocol violations. The final population was 282 patients. Intent-to-treat analyses were also performed for all major end points. The follow-up time was 5 years for all patients. RESULTS: Bone metastases were detected equally often in the clodronate and control groups: 29 patients (21%) versus 24 patients (17%) (P: = .27). The development of nonskeletal recurrence was significantly higher in the clodronate group compared with controls: 60 patients (43%) versus 36 patients (25%) (P: = .0007). The overall survival (OS) and disease-free survival (DFS) rates were also significantly lower in the clodronate group than in the controls (OS, 70% v 83%, P: = .009; DFS, 56% v 71%, P: = .007, respectively). In multivariate analyses, clodronate remained significantly associated with DFS (P: = .009). CONCLUSION: Adjuvant clodronate treatment does not prevent the development of bone metastases in node-positive breast cancer patients. However, clodronate seems to have a negative effect on DFS by increasing the development of nonskeletal metastases.
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Not sure how accurate this article is ...
" ... The molecular mechanisms by which tumor cells degrade bone involve tumor cell adhesion to bone as well as the release of toxic chemicals from tumor cells that stimulate osteoclast-induced bone degradation. Bisphosphonates inhibit both cancer-cell adhesion to the bone matrix and (as noted) osteoclast activity. By preventing tumor cell adhesion, biphosphonates are useful agents for the prophylactic treatment of patients with cancer that is known to preferentially metastasize to bone.
There is evidence that growth factors such as insulin-like growth factor and transforming growth factor are released when the bone matrix is degraded. These growth factors could stimulate tumor cell proliferation throughout the body, which may be a reason that early use of clodronate has significantly improved survival.
..."
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Ask the Drs about zometa or another biphosphonate. It is usually given for bone mets. It is sometimes given as a preventive measure, I think.
You could ask about the grade (aggressiveness) of the cancer. If it is a high grade tumor (aggressive). then I personally would push even harder for getting treatment. Even if it isnt I would try to get things going
Take care
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This is a monoclonal anti-body that targets VEGF. There have been problems though due to excess bleeding
http://www.gene.com/gene/pipeline/statu ... /index.jsp
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Guest,
When I saw your first message, I thought it said your doctor told your mom to *take* aspirin while receiving chemo.
As Sandy said Cox-2 it not a blood thinner
The link below, like the onc says do NOT take aspirin
http://www.clevelandclinic.org/health/h ... index=4942
sandy is right on this one. May decrease platlets. I think some other chemo's actually cause clotting.
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The aspirin though *may* interact with the particular chemo your mom is taking. LMWH, low molecular weight herepin, (a blood thinner) and chemo seem to increase survival.
Though aspirin and LMWH are both blood thinners the mechanism for thinnging the blood is probably different.
Take are
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It definitely is hard to figure out. As far as COX-2 I would ask the doctor. Make absolutely sure that COX-2 won't cause problems.
To add to the confusion there was a study that aspirin and platinum-based chemo actually helped.
http://www.countrydoctor.co.uk/educatio ... spirin.htm
Guess that's why doctors, at least oncs, spend 10+ years in school after college.
nicotine and lung cancer
in CLINICAL TRIALS
Posted
Another reason to stop smoking - even after one is diagnosed with lung cancer.
http://www.eurekalert.org/pub_releases/ ... 032603.php
Another research report ...
Synthesis of acetylcholine by lung cancer.
Song P, Sekhon HS, Proskocil B, Blusztajn JK, Mark GP, Spindel ER.
Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR 97006, USA.
The role of autocrine growth factors in the stimulation of lung cancer growth is well established. Nicotine is an agonist for acetylcholine receptors and stimulates lung cancer growth. This suggests that if lung cancers synthesize acetylcholine (ACh), then ACh may be an autocrine growth factor for lung cancer. Analysis of normal lung demonstrated that the cells of origin of lung cancers express the proteins necessary for non-neuronal ACh storage and synthesis. Analysis of mRNA from squamous cell lung carcinoma, small cell lung carcinoma (SCLC) and adenocarcinoma showed synthesis of choline acetyltransferase (ChAT) and nicotinic receptors. Immunohistochemical analysis of a retrospective series of SCLC and adenocarcinomas showed that more than 50% of the lung cancers screened expressed ChAT and nicotinic receptors. To study the effect of endogenous ACh synthesis on growth, SCLC cell lines were studied. SCLC cell lines were found to express ChAT mRNA and to secrete ACh into the medium as measured by HPLC separation and enzymatically-coupled electrochemical detection. The SCLC cell line NCI-H82 synthesized highest levels of ACh. Showing that the endogenously synthesized ACh interacted with its receptors to stimulate cell growth, addition of muscarinic and nicotinic antagonists slowed H82 cell proliferation. These findings demonstrate that lung cancer cell lines synthesize and secrete ACh to act as an autocrine growth factor. The existence of a cholinergic autocrine loop in lung cancer provides a basis for understanding the effects of nicotine in cigarette smoke on lung cancer growth and provides a new pathway to investigate for potential therapeutic approaches to lung cancer. Copyright 2003 Elsevier Science Inc.