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1.
Asia Pac J Clin Oncol ; 12(2): e222-8, 2016 Jun.
Article in English | MEDLINE | ID: mdl-24571381

ABSTRACT

AIMS: Perioperative chemotherapy has improved the prognosis for patients with operable osteosarcoma. The literature is conflicting about which regimen is optimal. The aim of this study was to evaluate the survival outcomes of two cohorts of patients with operable osteosarcoma treated with different perioperative chemotherapy regimens. METHODS: This was a retrospective review of patients diagnosed with operable osteosarcoma treated at the Princess Alexandra Hospital from 1986 to 2009. The standard perioperative chemotherapy regimen changed from the modified T10 Rosen protocol to cisplatin/doxorubicin in 1997. Using the Kaplan-Meier method, overall survival (OS) and disease-free survival (DFS) curves were generated for the cisplatin/doxorubicin and the modified T10 Rosen cohorts. RESULTS: Seventy-one patients were identified of whom 63 had potentially curable disease. Of these, 24 received the modified T10 Rosen regimen and 39 received cisplatin/doxorubicin. There was a non-significant trend toward better OS and DFS in the patients who received the modified T10 Rosen protocol. CONCLUSION: The trend toward poorer survival in the cisplatin/doxorubicin cohort, in combination with current evidence, has prompted our institution to change its practice.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Neoplasms/drug therapy , Bone Neoplasms/surgery , Osteosarcoma/drug therapy , Osteosarcoma/surgery , Adolescent , Adult , Aged , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Male , Middle Aged , Perioperative Care/methods , Prognosis , Retrospective Studies , Young Adult
2.
Trials ; 15: 191, 2014 May 28.
Article in English | MEDLINE | ID: mdl-24885486

ABSTRACT

BACKGROUND: Few cancers pose greater challenges than head and neck (H&N) cancer. Residual effects following treatment include body image changes, pain, fatigue and difficulties with appetite, swallowing and speech. Depression is a common comorbidity. There is limited evidence about ways to assist patients to achieve optimal adjustment after completion of treatment. In this study, we aim to examine the effectiveness and feasibility of a model of survivorship care to improve the quality of life of patients who have completed treatment for H&N cancer. METHODS/DESIGN: This is a preliminary study in which 120 patients will be recruited. A prospective randomised controlled trial of the H&N Cancer Survivor Self-management Care Plan (HNCP) involving pre- and post-intervention assessments will be used. Consecutive patients who have completed a defined treatment protocol for H&N cancer will be recruited from two large cancer services and randomly allocated to one of three study arms: (1) usual care, (2) information in the form of a written resource or (3) the HNCP delivered by an oncology nurse who has participated in manual-based training and skill development in patient self-management support. The trained nurses will meet patients in a face-to-face interview lasting up to 60 minutes to develop an individualised HNCP, based on principles of chronic disease self-management. Participants will be assessed at baseline, 3 and 6 months. The primary outcome measure is quality of life. The secondary outcome measures include mood, self-efficacy and health-care utilisation. The feasibility of implementing this intervention in routine clinical care will be assessed through semistructured interviews with participating nurses, managers and administrators. Interviews with patients who received the HNCP will explore their perceptions of the HNCP, including factors that assisted them in achieving behavioural change. DISCUSSION: In this study, we aim to improve the quality of life of a patient population with unique needs by means of a tailored self-management care plan developed upon completion of treatment. Delivery of the intervention by trained oncology nurses is likely to be acceptable to patients and, if successful, will be a model of care that can be implemented for diverse patient populations. TRIAL REGISTRATION: ACTRN12613000542796 (registered on 15 May 2013).


Subject(s)
Adaptation, Psychological , Head and Neck Neoplasms/nursing , Head and Neck Neoplasms/psychology , Oncology Nursing/methods , Quality of Life/psychology , Affect , Head and Neck Neoplasms/therapy , Humans , Pamphlets , Prospective Studies , Research Design , Self Care/methods , Self Care/psychology , Self Efficacy , Survivors/psychology
3.
BMC Complement Altern Med ; 14: 134, 2014 Apr 09.
Article in English | MEDLINE | ID: mdl-24712653

ABSTRACT

BACKGROUND: Preliminary research shows ginger may be an effective adjuvant treatment for chemotherapy-induced nausea and vomiting but significant limitations need to be addressed before recommendations for clinical practice can be made. METHODS/DESIGN: In a double-blinded randomised-controlled trial, chemotherapy-naïve patients will be randomly allocated to receive either 1.2 g of a standardised ginger extract or placebo per day. The study medication will be administrated as an adjuvant treatment to standard anti-emetic therapy and will be divided into four capsules per day, to be consumed approximately every 4 hours (300 mg per capsule administered q.i.d) for five days during the first three cycles of chemotherapy. Acute, delayed, and anticipatory symptoms of nausea and vomiting will be assessed over this time frame using a valid and reliable questionnaire, with nausea symptoms being the primary outcome. Quality of life, nutritional status, adverse effects, patient adherence, cancer-related fatigue, and CINV-specific prognostic factors will also be assessed. DISCUSSION: Previous trials in this area have noted limitations. These include the inconsistent use of standardized ginger formulations and valid questionnaires, lack of control for anticipatory nausea and prognostic factors that may influence individual CINV response, and the use of suboptimal dosing regimens. This trial is the first to address these issues by incorporating multiple unique additions to the study design including controlling for CINV-specific prognostic factors by recruiting only chemotherapy-naïve patients, implementing a dosing schedule consistent with the pharmacokinetics of oral ginger supplements, and independently analysing ginger supplements before and after recruitment to ensure potency. Our trial will also be the first to assess the effect of ginger supplementation on cancer-related fatigue and nutritional status. Chemotherapy-induced nausea and vomiting are distressing symptoms experienced by oncology patients; this trial will address the significant limitations within the current literature and in doing so, will investigate the effect of ginger supplementation as an adjuvant treatment in modulating nausea and vomiting symptoms. TRIAL REGISTRATION: ANZCTR.org.au Identifier: ACTRN12613000120774.


Subject(s)
Antiemetics/administration & dosage , Antineoplastic Agents/adverse effects , Nausea/drug therapy , Neoplasms/drug therapy , Plant Extracts/administration & dosage , Zingiber officinale/chemistry , Antineoplastic Agents/therapeutic use , Clinical Protocols , Double-Blind Method , Humans , Nausea/etiology , Quality of Life , Surveys and Questionnaires , Vomiting/chemically induced , Vomiting/drug therapy
4.
Nutr Rev ; 71(4): 245-54, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23550785

ABSTRACT

Chemotherapy-induced nausea and vomiting (CINV) is a common side-effect of cytotoxic treatment. It continues to affect a significant proportion of patients despite the widespread use of antiemetic medication. In traditional medicine, ginger (Zingiber officinale) has been used to prevent and treat nausea in many cultures for thousands of years. However, its use has not been confirmed in the chemotherapy context. To determine the potential use of ginger as a prophylactic or treatment for CINV, a systematic literature review was conducted. Reviewed studies comprised randomized controlled trials or crossover trials that investigated the anti-CINV effect of ginger as the sole independent variable in chemotherapy patients. Seven studies met the inclusion criteria. All studies were assessed on methodological quality and their limitations were identified. Studies were mixed in their support of ginger as an anti-CINV treatment in patients receiving chemotherapy, with three demonstrating a positive effect, two in favor but with caveats, and two showing no effect on measures of CINV. Future studies are required to address the limitations identified before clinical use can be recommended.


Subject(s)
Antiemetics/therapeutic use , Nausea/therapy , Plant Extracts/therapeutic use , Vomiting/therapy , Zingiber officinale/chemistry , Antineoplastic Agents/adverse effects , Humans , Nausea/chemically induced , Neoplasms/drug therapy , Randomized Controlled Trials as Topic , Treatment Outcome , Vomiting/chemically induced
5.
Eur J Cancer ; 47(3): 354-60, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21084184

ABSTRACT

INTRODUCTION: Preoperative chemotherapy (CT) and preoperative chemoradiation therapy (CRT) for resectable oesophageal cancer have been shown to improve overall survival in meta-analyses. There are limited data comparing these preoperative therapies. We report the outcomes of a randomised phase II trial comparing preoperative CT and CRT for resectable adenocarcinoma of the oesophagus and gastro-oesophageal junction. METHODS: Patients were randomised to receive preoperative CT with cisplatin (80 mg/m(2)) and infusional 5 fluorouracil (1000 mg/m(2)/d) on days 1 and 21, or preoperative CRT with the same drugs accompanied by concurrent radiation therapy commencing on day 21 of chemotherapy and the 5 fluorouracil reduced to 800 mg/m(2)/d. The radiation dose was 35 Gy in 15 fractions over 3 weeks. The endpoints were toxicity, response rates, resection (R) status, progression-free survival (PFS), overall survival (OS) and quality of life. RESULTS: Seventy-five patients were enrolled on the study: 36 received preoperative CT and 39 preoperative CRT. Toxicity was similar for CT and CRT. Eight patients (11%) did not proceed to resection. The histopathological response rate (CRT 31% versus CT 8%, p = 0.01) and R1 resection rate (CRT 0% versus CT 11%, p = 0.04) favoured those receiving CRT. The median PFS was 14 and 26 months for CT and CRT respectively (p = 0.37). The median OS was 29 months for CT compared with 32 months for CRT (p = 0.83). CONCLUSIONS: Despite no difference in survival, the improvement from preoperative CRT with respect to margin involvement makes this treatment a reasonable option for bulky, locally advanced resectable adenocarcinoma of the oesophagus.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/radiotherapy , Adenocarcinoma/surgery , Adult , Aged , Cisplatin/administration & dosage , Cisplatin/adverse effects , Disease-Free Survival , Esophageal Neoplasms/surgery , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Male , Middle Aged , Neoadjuvant Therapy/adverse effects , Neoadjuvant Therapy/methods , Neoplasm Recurrence, Local/etiology , Postoperative Complications/etiology , Radiotherapy/adverse effects , Treatment Outcome
6.
J Natl Cancer Inst ; 102(16): 1253-62, 2010 Aug 18.
Article in English | MEDLINE | ID: mdl-20631341

ABSTRACT

BACKGROUND: The Australian and New Zealand Germ Cell Trials Group conducted a multicenter randomized phase III trial in men with good-prognosis germ cell tumors of two standard chemotherapy regimens that contained bleomycin, etoposide, and cisplatin but differed in the scheduling and total dose of cisplatin, the total dose of bleomycin, and the scheduling and dose intensity of etoposide. The trial was stopped early at a median follow-up of 33 months after a planned interim analysis found a survival benefit for the more dose-intense regimen. The aim of this analysis was to determine if this survival benefit was maintained with long-term follow-up. METHODS: Between February 1994 and April 2000, 166 men with good-prognosis metastatic germ cell tumors defined by modified Memorial Sloan-Kettering criteria were randomly assigned to receive 3B(90)E(500)P (three cycles, repeated every 21 days, of 30 kU bleomycin on days 1, 8, and 15; 100 mg/m(2) etoposide on days 1-5; and 20 mg/m(2) cisplatin on days 1-5; n = 83) or 4B(30)E(360)P (four cycles, repeated every 21 days, of 30 kU bleomycin on day 1, 120 mg/m(2) etoposide on days 1-3, and 100 mg/m(2) cisplatin on day 1; n = 83). Endpoints included overall survival, progression-free survival, and quality of life and side effects, which were assessed using the Spitzer Quality of Life Index and the GLQ-8, respectively, before random assignment and during and after treatment. All analyses were by intention to treat. All P values are two-sided. RESULTS: The median follow-up was 8.5 years. All but five survivors (3%) were followed up for at least 5 years. Overall survival remained better in those assigned to 3B(90)E(500)P than in those assigned to 4B(30)E(360)P (8-year survival: 92% vs 83%; hazard ratio of death = 0.38, 95% confidence interval = 0.15 to 0.97, P = .037). Progression-free survival favored 3B(90)E(500)P but was not statistically significantly different between the treatment groups (8-year progression-free survival, 3B(90)E(500)P vs 4B(30)E(360)P: 86% vs 79%; hazard ratio of progression = 0.6, 95% confidence interval = 0.3 to 1.1, P = .15). At the end of treatment, average scores for most side effect scales favored 3B(90)E(500)P. After the completion of treatment, average GLQ-8 scores for numbness (P = .003) and hair loss (P = .04) and the Spitzer Quality of Life Index (P = .05) favored 3B(90)E(500)P. CONCLUSION: The survival benefit of 3B(90)E(500)P over 4B(30)E(360)P was maintained with long-term follow-up.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Neoplasms, Germ Cell and Embryonal/drug therapy , Testicular Neoplasms/drug therapy , Adolescent , Adult , Australia , Bleomycin/administration & dosage , Cisplatin/administration & dosage , Disease-Free Survival , Dose-Response Relationship, Drug , Drug Administration Schedule , Etoposide/administration & dosage , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Neoplasms, Germ Cell and Embryonal/secondary , New Zealand , Prognosis , Quality of Life , Seminoma/drug therapy , Testicular Neoplasms/pathology , Treatment Outcome , Young Adult
7.
Radiother Oncol ; 90(2): 172-6, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18976827

ABSTRACT

PURPOSE: To report toxicity data from the first 13 consecutive patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC), ineligible for cisplatin, treated with concurrent cetuximab and radiotherapy (RT) at our institution. MATERIALS AND METHODS: Data were collected prospectively between August 2007 and May 2008. Planned treatment consisted of a cetuximab loading dose (400mg/m(2)) via intravenous infusion 1 week prior and then weekly (250mg/m(2)) with 70Gy in 35 daily fractions over 7 weeks. RESULTS: Median age was 68 years (range 52-82 years). The predominant primary sites were hypopharyngeal (5) and oropharyngeal (5). Ineligibility for cisplatin consisted of renal impairment (5), hearing impairment (4) and of other major co-morbidities (4). Of the 13 patients, 10 (77%) had grade 3/4 skin reactions and 10 (77%) grade 3/4 mucositis. Six (46%) patients required admission for management of severe skin reactions and/or mucositis with 4 (31%) requiring a treatment break, median 10 days (9-15days). Only 4 (31%) patients managed to complete the planned 8 cycles of cetuximab. Of the 9 patients with 12-week post-therapy data, 7 (78%) achieved a complete response. CONCLUSIONS: Our early experience with cetuximab/RT has demonstrated a higher rate of toxicity compared with the recently reported randomised trial, resulting in low treatment compliance and delays in completing RT.


Subject(s)
Antibodies, Monoclonal/adverse effects , Antineoplastic Agents/adverse effects , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Otorhinolaryngologic Neoplasms/drug therapy , Otorhinolaryngologic Neoplasms/radiotherapy , Radiodermatitis/pathology , Aged , Aged, 80 and over , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/therapeutic use , Cetuximab , Combined Modality Therapy , Drug Eruptions/etiology , Drug Eruptions/pathology , Epidermal Growth Factor/antagonists & inhibitors , Female , Humans , Male , Middle Aged , Radiotherapy Dosage
8.
Invest New Drugs ; 27(3): 275-9, 2009 Jun.
Article in English | MEDLINE | ID: mdl-18841327

ABSTRACT

BACKGROUND: Chemoradiation therapy using regimens containing cisplatin and 5-fluorouracil are most commonly used for inoperable cancer of the esophagus. Cisplatin is relatively toxic and is not suitable for many patients. Little data exists using platinum analogues together with protracted infusion 5-fluorouracil and radiation therapy in the curative setting. METHODS: Fourteen patients with localised oesophageal cancer suitable for curative chemoradiation therapy registered on the study. Chemotherapy consisted of 5-fluorouracil 225 mg/m(2) daily throughout radiation therapy, with oxaliplatin 60 mg/m(2) weekly. The radiation dose was 56 to 60 Gy in 28 to 30 fractions. RESULTS: The median age of the patients was 70.5 years. Therapy was associated with excessive grade 3 and 4 non-hematologic toxicity. There was one treatment related death. The median progression-free survival was 31.5 months and median overall survival 32.6 months. Six patients achieved a prolonged complete endoscopic and radiological response. CONCLUSIONS: Although weekly oxaliplatin in combination with infusional 5 fluorouracil produces durable remissions in esophageal cancer, the regimen used in this trial was not acceptable for routine use. Future protocols should incorporate lower chemotherapy doses.


Subject(s)
Antineoplastic Agents/therapeutic use , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/radiotherapy , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/therapeutic use , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease-Free Survival , Drug Administration Schedule , Female , Fluorouracil/adverse effects , Humans , Infusions, Intravenous , Male , Middle Aged , Oxaliplatin
9.
Ann Surg Oncol ; 15(10): 2894-902, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18663531

ABSTRACT

OBJECTIVE: Accurate staging is vital for esophageal cancer management. The utility of the American Joint Committee on Cancer (AJCC) staging system 6th edition for esophageal cancer has been questioned for resected patients who receive neoadjuvant chemoradiotherapy (CRT). This study was undertaken to assess the AJCC staging system for patients with esophageal cancer that have received neoadjuvant CRT and to identify clinicopathological variables that predict survival. METHODS: Review of a prospective esophageal cancer database was undertaken for patients that received neoadjuvant CRT and resection. Primary tumor response was defined as major (10% residual tumor cells). Cox regression and concordance analyses were used to determine prognostic factors. Median follow-up was 61 months. RESULTS: Of 131 patients with invasive cancer, there were 40/131 (31%) with squamous cell carcinoma (SCC) and 88/131 (65%) with adenocarcinoma. The procedure-related mortality rate was 3.8%. Median survival was 33 months. A major response was demonstrated by 79/131 (60%) patients. Survival analyses found that the AJCC 6th edition was unable to discriminate between stages 0, I, and IIa or stages IIb and III. Multivariate survival analyses found age, pretreatment tumor length >6 cm, positive lymph nodes, and a major tumor response were independent prognostic factors. These data were used to derive a new staging system that had improved discrimination of stage groups over the current AJCC system. CONCLUSION: The current AJCC staging system for esophageal cancer is inadequate for patients that receive neoadjuvant CRT. Refinement of the AJCC staging system should include primary tumor response for patients receiving neoadjuvant CRT.


Subject(s)
Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Esophagogastric Junction/pathology , Neoadjuvant Therapy , Adenocarcinoma/secondary , Adenocarcinoma/therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/secondary , Carcinoma, Squamous Cell/therapy , Chemotherapy, Adjuvant , Combined Modality Therapy , Esophagectomy , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Prospective Studies , Radiotherapy, Adjuvant , Survival Rate , Treatment Outcome
10.
Invest New Drugs ; 26(1): 89-94, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17891338

ABSTRACT

Treatment options for advanced melanoma are limited. PI-88, a potent inhibitor of heparanase, demonstrates anitangiogenic properties and has shown activity against melanoma in phase I studies. This was an open-label, multicenter, phase II study of PI-88 in patients with advanced melanoma. Patients received a fixed-dose of 250 mg/day given subcutaneously for four consecutive days followed by three drug-free days per week in a 28-day cycle. A total of 44 patients were enrolled in the intent to treat population, with 59.1% having received previous therapy. The median time to progression and overall survival was 1.7 months and 9 months, respectively. Forty-one patients are included in the efficacy analysis. One (2.4%) patient achieved a partial response, six (14.6%) patients had stable disease as best response, and 30 (73.2%) had progressive disease. At the end of six cycles of treatment, three of the 41 evaluable patients had non-progressive disease. Treatment was generally well tolerated. Injection site bruising occurred in 45% of patients. Serious bleeding did occur in two patients and three patients developed a positive anti-platelet antibody test during the study. One of these four patients experienced an associated thrombosis. In patients with advanced melanoma, PI-88 demonstrates an overall survival and time to progression similar to standard chemotherapy. Although the current study did not meet the primary end-point of progression free survival of >or=20%, there is some evidence of activity and further investigation is warranted.


Subject(s)
Glucuronidase/antagonists & inhibitors , Melanoma/drug therapy , Oligosaccharides/therapeutic use , Adult , Aged , Alanine Transaminase/blood , Contusions/etiology , Drug Administration Schedule , Fatigue/chemically induced , Female , Humans , Injections, Subcutaneous/adverse effects , Kaplan-Meier Estimate , Male , Melanoma/pathology , Middle Aged , Nausea/chemically induced , Neoplasm Metastasis , Oligosaccharides/administration & dosage , Oligosaccharides/adverse effects , Pain/etiology , Severity of Illness Index , Thrombocytopenia/chemically induced , Treatment Outcome
11.
Int J Clin Oncol ; 10(4): 256-61, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16136371

ABSTRACT

BACKGROUND: Chemoradiation therapy is the standard treatment for esophageal cancer in patients not fit for surgery. The regimen most commonly used includes cisplatin and 5-fluorouracil. Little data exists regarding alternative chemotherapy regimens in patients not suitable for cisplatin. We report on a regimen using protracted infusion 5-fluorouracil alone for both curative and palliative indications. METHODS: Twenty-two patients with localized esophageal cancer suitable for curative chemoradiation therapy and 24 patients suitable for palliative therapy were enrolled. Chemotherapy consisted of 5-fluorouracil 225 mg/m(2) daily throughout the radiation therapy. The radiation dose was 56 to 60 Gy in 28 to 30 fractions (curative patients) and 30 to 35 Gy in 15 fractions (palliative patients). RESULTS: The median age of the patients was 75 years. The regimen was tolerable. Significant grade 3 toxicities experienced were esophagitis (11%) and venous catheter toxicity (9%). The median survival was 17 months for curative patients and 9 months for palliative patients. The complete response rate was 86% endoscopically and 45% radiologically for curative patients. Relief of dysphagia was experienced in 67% of palliative patients. Quality of life was satisfactory in both groups. CONCLUSIONS: This study showed that continuous-infusion 5-fluorouracil given concurrently with radiation therapy is a useful alternative to platinum-based chemoradiation therapy in patients with esophageal carcinoma.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/radiotherapy , Fluorouracil/therapeutic use , Salvage Therapy , Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Adenocarcinoma/secondary , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/secondary , Combined Modality Therapy , Drug Administration Schedule , Esophageal Neoplasms/pathology , Feasibility Studies , Female , Humans , Lymphatic Metastasis/prevention & control , Male , Middle Aged , Quality of Life , Survival Rate
12.
Invest New Drugs ; 23(3): 253-6, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15868382

ABSTRACT

PURPOSE: To determine the activity and tolerability of SAM496A, an inhibitor of S-adenosylmethionine decarboxylase (SAMDC), in patients with metastatic melanoma who had not received prior chemotherapy. Selected patients were offered participation in two sub-studies examining early changes in tumor metabolism with FDG-PET and changes in tumor polyamine content. PATIENTS AND METHODS: Fifteen patients with measurable metastatic melanoma, normal cardiac function, and no known CNS metastases were eligible and received SAM486A by 1-hour IV infusion daily for 5 days every 3 weeks. Response was assessed by SWOG criteria. RESULTS: No patient had a confirmed partial response. Fatigue/lethargy, myalgia and neutropenia were the main toxicities but no febrile neutropenia or grade 4 non-hematological toxicity occurred. Five patients had PET scans pre-treatment and on days 8-12 of cycle 1. No patient had reduction of tumor metabolism. Serial biopsy in one patient showed alterations in polyamines consistent with SAMDC inhibition. CONCLUSIONS: Using the present dose and schedule of administration, SAM486A does not have significant therapeutic potential in patients with metastatic melanoma.


Subject(s)
Adenosylmethionine Decarboxylase/antagonists & inhibitors , Amidines/therapeutic use , Antineoplastic Agents/therapeutic use , Indans/therapeutic use , Melanoma/drug therapy , Melanoma/pathology , Adult , Aged , Amidines/adverse effects , Antineoplastic Agents/adverse effects , Female , Fluorodeoxyglucose F18 , Humans , Indans/adverse effects , Karnofsky Performance Status , Male , Melanoma/diagnostic imaging , Middle Aged , Neoplasm Metastasis , Positron-Emission Tomography , Radiopharmaceuticals
13.
Transpl Int ; 16(7): 529-36, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12734646

ABSTRACT

Post-transplant lymphoproliferative disorder (PTLD) complicates 1 to 10% of all transplantations. Previous clinicopathological studies of PTLD have been limited by small numbers, short follow-up times, outdated data, heterogeneity of pooled solid-organ transplant results, and selective inclusion of early-onset disease. We therefore undertake here a retrospective analysis and identify all cases of PTLD that complicated renal transplantation at the Princess Alexandra Hospital between 30 June 1969 and 31 May 2001. Tumour samples were subsequently retrieved for pathological review and for Epstein-Barr virus-encoded RNA in situ hybridisation (EBER-ISH). Of 2,030 renal transplantation patients, 29 (1.4%) developed PTLD after a median period of 0.5 years (range 0.1 to 23.3 years). PTLD patients were more likely to have received cyclosporine (76% versus 62%, P<0.05), tacrolimus (10% versus 2%, P<0.05) and OKT3 (28% versus 10%, P<0.01). As the burden of immunosuppression increased from dual, to triple, to OKT3 therapy, the risks of early onset, extensive-stage, polymorphic, Epstein-Barr virus (EBV)-associated and fatal PTLD progressively increased. The majority of patients presented with an extra-nodal mass (45%), were afebrile (76%), and had stage-IV disease (60%). EBER-ISH was positive in 58%. Actuarial 5-year disease-free survival was 53.7%. The independent predictors of mortality on multivariate Cox regression were polymorphic histology (HR 7.4, 95% CI 1.5-37) and an international prognostic index (IPI) >1 (HR 2.7, 95% CI 1.1-6.8). Compared with other treatments, chemotherapy was associated with higher survival rates (100% versus 18% at 3 years, P=0.0001). In conclusion, PTLD is more likely, occurs earlier, and is more often fatal, in the setting of intensive immunosuppression. Nevertheless, excellent long-term outcomes are achievable with early recognition and institution of appropriate treatment.


Subject(s)
Kidney Transplantation/adverse effects , Lymphoproliferative Disorders/etiology , Humans , Immunosuppression Therapy , Lymphoproliferative Disorders/pathology , Lymphoproliferative Disorders/therapy , Prognosis , Retrospective Studies , Survival Analysis
14.
Br J Haematol ; 119(2): 412-6, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12406079

ABSTRACT

Re-treatment with rituximab for B-cell non-Hodgkin's lymphoma (NHL) relapsing after previous rituximab therapy has recently been shown to be clinically efficacious. Although the mechanism of resistance to rituximab re-treatment in non-responding patients is unknown, it is possible that loss of CD20 expression in the relapsed NHL could be important in some patients. We examined the incidence and nature of CD20 negative relapses following rituximab therapy in aggressive B-cell NHL treated at our institution. Of a total of 18 patients who received rituximab, 13 have relapsed, with 10 patients subsequently undergoing repeat tissue biopsy. Six of these 10 patients (60%) were shown to have lost CD20 expression by either immunohistochemistry and/or flow cytometry. Furthermore, three of the six patients who relapsed with CD20-negative NHL also suffered relapses at unusual anatomical sites. We conclude that loss of CD20 expression in aggressive B-cell NHL relapsing post-rituximab therapy is common. As such, repeat tissue biopsy should be undertaken to document CD20 expression by both flow cytometry and immunohistochemistry prior to considering repeated courses of rituximab in relapsed aggressive lymphomas.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antigens, CD20/analysis , Antineoplastic Agents/therapeutic use , Lymphoma, B-Cell/immunology , Neoplasm Recurrence, Local/immunology , Adult , Aged , Antibodies, Monoclonal, Murine-Derived , Antigens, CD20/immunology , Female , Flow Cytometry , Humans , Immunohistochemistry , Incidence , Lymphoma, B-Cell/drug therapy , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Retrospective Studies , Rituximab
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