Chemotherapy with etoposide,doxorubicin, cisplatin, 5-fluorouracil,and leucovorin for patients with advanced hepatocellular carcinoma

BACKGROUND: To investigate the therapeutic index of combining etoposide, doxorubicin (adriamycin), cisplatin, 5-fluorouracil (5-FU), and leucovorin (EAPFL) chemotherapy in the treatment of advanced HCC, a trial of a novel schedule of triweekly administration was conducted. PATIENTS AND METHODS: Sixty-six patients with measurable advanced HCC, adequate liver and renal functions and adequate bone marrow reserves in whom local treatment was not indicated were studied. Triweekly EAPFL treatment consisted of a concomitant boost of etoposide 40 mg/m2 i.v. over 30 min on day 1, 2, and 3, doxorubicin 30 mg/m2 i.v. over 30 min on day 1 to a backbone regimen, triweekly PFL chemotherapy with cisplatin 60 mg/m2, 5-FU 1,200 mg/m2, and leucovorin 120 mg/m2 given simultaneously by a 72-h i.v. infusion. Response, survival, and toxicity were evaluated. RESULTS: One patient had complete response (1%) and thirteen patients had partial response (20%). The objective response rate was 21% (95% confidence interval 11-31%). The median overall survival and median time to progression were 8.9 months and 3.3 months, respectively. Major treatment toxicities (grade 3-4) were neutropenia (28%), anemia (11%), thrombocytopenia (7%), hepatotoxicity (5%), vomiting (2%), and diarrhea (2%). There was no treatment-related death. CONCLUSION: Triweekly EAPFL chemotherapy is a moderately effective regimen with tolerable toxicities in the treatment of advanced HCC.     

Adjuvant chemotherapy with adriamycin, fluorouracil, cyclophosphamide, methotrexate, with or without tamoxifen in operable breast cancer

Between January 1982 and February 1985, 70 breast cancer patients with histologically confirmed axillary node involvement and T1-3a were treated following surgery with a combination of adriamycin, fluorouracil, cyclophosphamide, methotrexate, with or without tamoxifen according to the estrogen and progesterone receptors state. At 60 months of study (median follow-up, 41 months), the estimated proportion remaining disease-free was 62%. The estimated survival rate was 81%. A comparison of the actuarial disease-free and overall survival with data reported in the literature indicates a similar positive effect of adjuvant systemic therapy as described in adjuvant studies using polychemotherapy regimens. Patient acception of chemotherapy regimen was generally good. This can be accounted for because of an adequate emesis control and real compliance of the patients with the oncologist.     

Stigma,self-blame,and satisfaction with care among patients with lung cancer

Objective: We sought to understand the experiences of patients with lung cancer and to see if attitudes varied by demographic factors. Methods: We administered a 63-question survey by phone or online among 174 patients with lung cancer. Factor analysis was used to identify two groups of questions with a conceptual relationship and high Cronbach's alphas, stigma and satisfaction with care. We used a multivariable analysis to identify predictors of self-blame and the factors of stigma and satisfaction with care. Results: Patients were satisfied with the quality of their care and treatment choices but did not feel that there is enough public support for or research in lung cancer. Predictors of lower satisfaction with care were never being a smoker, lack of college education, not living in a rural location, refusing to report income, and not knowing/not being sure of stage. Self-blame was modest; in multivariable analysis, predictors of self-blame were believing that smoking was a cause of their lung cancer, younger age, male sex, living in a suburban location, and not knowing/not being sure of the stage of the cancer. Reported stigma was low and the only predictor for stigma was being married. Despite low scores on their personal experience of stigma, patients reported a high degree of stigmatization of lung cancer in general. Smoking was a significant predictor of personal stigma. Conclusion: Despite satisfaction with their treatment and care, lung cancer patients feel that society stigmatizes them as a general population. Patients who smoke are more likely to report that they have personally experienced stigma.     

Survival of women with breast cancer in Ottawa, Canada: variation with age, stage, histology, grade and treatment

This study examined the 5-year survival of 2192 breast cancer women diagnosed between 1994 and 1997 in Ottawa, Canada, by age, TNM stage, histology, grade and treatment, including assessment of the independent value of variables in defining prognosis. Our results showed that age, stage, treatment and grade significantly influenced outcome regardless of the confounding factors considered, with histology failing to achieve significant independent prognostic information. The survival rates were highest at ages 50-69 years for stage I and at ages 40-49 years for stages II-IV. The rates were lowest at ages or=70 years for stages III-IV. The differences in survival between grade 1 and grade 3 were 9% in stage I and 20% in stage II. The treatment leading to the best survival was surgery plus radiation for stages I-II and surgery combined with chemotherapy for stages III-IV. Lobular carcinoma had a better prognosis than ductal carcinoma; this can be explained by more grade 1 and less grade 3 cases in lobular carcinoma. The worse prognosis for young patients than other ages can be explained by their higher proportion of poorly differentiated cancers. Stage I patients aged 50-69 years having the best survival is likely due to the earlier diagnosis achieved through screening.     

Biochemotherapy with temozolomide, cisplatin, vinblastine, subcutaneous interleukin-2 and interferon-alpha in patients with metastatic melanoma

The aim of this study was to determine the efficacy and tolerability of a biochemotherapy regimen, including low-dose subcutaneous interleukin-2 and temozolomide, in patients with metastatic melanoma. Treatment consisted of temozolomide (150 mg/m per day on days 1-5), cisplatin (20 mg/m per day intravenously on days 1-4), vinblastine (1.5 mg/m per day on days 1-4), interleukin-2 (4.5 MU/m per day subcutaneously on days 5-8) and interferon-alpha2b (5 MU subcutaneously on days 5-9, 11, 13, 15, every 28 days). Thirty-six patients were included. Patients with poor prognostic factors were not excluded. Seventeen patients (47%) had been treated previously in an adjuvant setting with interferon-alpha. Four patients (11%) had been treated previously with chemotherapy and six (17%) had been treated with other biochemotherapy regimens. The distribution by American Joint Committee on Cancer staging was as follows: M1a in two patients (6%), M1b in 11 patients (31%) and M1c in 23 patients (64%). At inclusion, seven patients (19.4%) had cerebral metastases that had previously been treated with whole brain radiotherapy. For thirty-four evaluable patients, seven (20.5%) achieved an objective response. Overall, metastatic disease was substantially decreased or temporarily stabilized in 11 patients (32.4%; 95% confidence interval, 17.4-50.5). Responses were observed for all locations. The central nervous system was the initial site of relapse in two responding patients. The median survival was 10 months. The main toxicities noted were haematological (grades 3-4): neutropenia (1.8%), thrombocytopenia (1.8%) and anaemia (1.2%). It can be concluded that this regimen is well tolerated and has a modest activity despite the poor prognosis of our patient population. The low haematological toxicity rate obtained suggests that higher doses could be tried.     

Combination chemotherapy with cyclophosphamide,vincristine, procarbazine,and prednisone (COPP) in children with brain tumors

Summary The chemotherapeutic combination of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) was used to treat 15 children with recurrent central nervous system tumors and seven children with newly diagnosed brainstem tumors. In patients with recurrent tumors, marginal activity was seen in various histologic types. COPP chemotherapy was clearly ineffective in patients with brainstem tumors. Toxicity consisted of mild to moderate myelosuppression and neurotoxicity.     

Evaluation of dose-intense Ifosfamide, with and without edatrexate, in adults with sarcoma

Purpose. To define the maximally tolerated dose (MTD) of ifosfamide when given with G-CSF on an every other week schedule, and to define the MTD of edatrexate that can be given every two weeks with an intense schedule of ifosfamide.Patients and Methods. Forty-one patients with metastatic or unresectable, locally advanced sarcoma participated in this 2-step phase I trial.The starting dose of ifosfamide was 10 gm/m(2) given by continuous intravenous infusion over 4 days every 2 weeks.When the MTD was defined, edatrexate, beginning at a dose of 40 mg/m(2) intravenously every 2 weeks was added in subsequent cohorts of patients.Results. Myelosuppression was the most prominent toxicity. Fatigue, nausea, and vomiting were observed in the majority of patients. Ifosfamide 12 gm/m(2) given every 2 weeks approached or exceeded the MTD. Edatrexate 100 mg/m(2) could be given safety as an intravenous bolus with ifosfamide 10 gm/m(2) every 2 weeks. Therapeutic responses were observed in patients with measurable disease.Conclusions. This study demonstrates the feasibility of administering a dose-intense schedule of ifosfamide alone or ifosfamide with edatrexate that might be applied in the adjuvant or neo-adjuvant setting.     

Acute promyelocytic leukemia, hypogranular variant, with uncharacteristic staining with chloroacetate esterase.

A diagnosis of the hypogranular variant of acute promyelocytic leukemia (APLv) may be difficult to establish based on cytomorphology alone. However, the great majority of cases have a classical immunophenotype by flow cytometric immunophenotyping (FCI) (CD13+, CD33+, dim CD64+, HLA-DR-, and CD34-) and a classical enzyme cytochemical (EC) staining pattern. [intensely staining with myeloperoxidase, Sudan Black B, and chloroacetate esterase (CAE) and negative with alpha'-naphthyl acetate and butyrate esterases]. Although the immunophenotype of APLv by FCI has varied in the literature (HLA-DR +/- and CD34 +/-), the EC staining pattern has remained constant. We report a case of APLv with characteristic cytomorphology, compatible FCI data (CD13+, CD33+, dim CD64+, HLA-DR +/-, and CD34-), chromosomal detection of t(15; 17), and molecular detection of the PML/RAR alpha fusion gene; however, staining of the leukemic cells with CAE was quite uncharacteristic. We describe our findings.     

Chemotherapy with etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone in patients with refractory cutaneous T-cell lymphoma.

BACKGROUND: This Phase II study was undertaken to assess the efficacy and toxicity of chemotherapy with etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone (EPOCH regimen) in patients with advanced, refractory cutaneous T-cell lymphoma (CTCL). METHODS: Fifteen patients were treated with a 96-hour continuous infusion of etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone, followed by granulocyte-colony stimulating factor support and trimethoprim/sulfamethoxazole prophylaxis. The median age of the patients was 53 years (range, 17-82 years). Six patients had Sézary syndrome (SS), four patients had visceral involvement, and four patients had anaplastic large cell morphology, three with Ki-1 (CD30) positivity. All patients had disease that was refractory to prior chemotherapy or electron beam irradiation and eight of these patients had received cyclophosphamide, doxorubicin, vincristine, and prednisone. Seven patients had received prior interferon therapy and nine patients had received fludarabine and/or 2-CDA. RESULTS: After a median of 5 cycles (range, 1-9 cycles), 4 patients achieved a complete response (27%) and 8 patients achieved a partial response (53%) for an overall response rate of 80% (95% confidence interval, 52-96%). Three patients with visceral involvement, two of three patients with anaplastic large cell morphology, and one patient with human T-cell lymphoma virus leukemia/lymphoma did not respond. All 12 responders had improvement in skin disease; 2 of 6 patients with SS had complete disappearance of circulating Sézary cells. The median progression free survival was 8.0 months (range, 3-22 months). After a median follow-up of 11.4 months (range, 2-56+ months), the median patient survival was 13.5 months. Grade 3 or 4 hematologic toxicity occurred in 8 patients (61%); 5 of these 8 patients had febrile neutropenia. Six patients developed staphylococcal bacteremia, two patients had disseminated herpes infection, and one patient had Pneumocystis carinii pneumonia. Grade 3 neurotoxicity occurred in one patient. Two patients had a significant decrease in left ventricular ejection fraction and one patient had supraventricular tachycardia. CONCLUSIONS: EPOCH chemotherapy has a high response rate with acceptable toxicity in patients with advanced and refractory CTCL.     

Dying with cancer, living well with advanced cancer

Introduction. There are 1.7 million deaths from cancer in Europe each year and by 2020 the World Health Organisation (WHO) estimates that, globally, more than 15 million people will experience cancer and 10 million will die from it each year. Furthermore, as new therapies are developed, people are living longer with cancer than in the past, and the population with cancer will be older.Materials and methods. We used epidemiologically based needs assessment approaches to estimate the number of people in Europe with symptoms and problems, published data and reviews to appraise treatment options, issues of communication, family care, bereavement and socio-demographic factors affecting care, and a European survey to consider the types of services. In addition, we used systematic literature review data to appraise the effectiveness of services and factors affecting place of death.Results. The quality of life of virtually all cancer patients with advanced disease is impaired by one or more symptoms, emotional, social, spiritual and communication concerns. Patients have a median of 11 symptoms. In Europe there are up to 1.6 million patients with pain each year, and in around one third of these it will be severe, requiring complex treatment. Almost an equal number are affected by fatigue, and more than 1 in 2 are affected by anxiety and/or depression, breathlessness, insomnia, nausea, constipation and/or anorexia. There is a complex interaction of factors affecting place of death – related to illness, the individual and environment – and although most people want to die at home, in most countries the majority of cancer patients die in hospital. In response to patient and family needs, systematic review shows the effectiveness of palliative care services. However, the distribution of services across Europe is inequitable.Conclusion. Palliative care is becoming increasingly recognised as a vital component of cancer care, but requires investment in research, education and services, incorporating appropriate needs assessment and outcome measurements.     

Clinical experience with intravenous estramustine phosphate, paclitaxel, and carboplatin in patients with castrate, metastatic prostate adenocarcinoma

BACKGROUND: The combination of paclitaxel, oral estramustine phosphate (EMP), and carboplatin (TEC) has shown antitumor activity in patients with castrate, metastatic prostate carcinoma. To improve the therapeutic efficacy and reduce the toxicity of TEC, the authors substituted intravenous (i.v.) EMP for oral EMP based on single-agent studies demonstrating an improved safety profile with i.v. EMP. METHODS: Patients with progressive, castrate, metastatic prostate carcinoma were treated with up to 6 4-week cycles of i.v. EMP (500-1500 mg/m(2) per week), paclitaxel (100 mg/m(2) per week), and carboplatin (target area under the curve = 6 mg/mL every 4 weeks). RESULTS: Thirty patients were treated in 6 dose cohorts. Deep venous thrombosis occurred in 5 of 30 patients (17%). Other common Grade 3/4 (according to National Cancer Institute Common Toxicity Criteria) toxicities included hepatic toxicity (23%) and leukopenia (24%). Posttherapy prostate specific antigen declines > 50% were seen in 18 of 30 patients (60%), and declines > 80% were seen in 15 of 30 patients (50%). Eleven of 17 patients (65%) with measurable soft tissue disease achieved a partial response. Four of 27 patients (15%) with osseous metastases demonstrated improvement on bone scan. CONCLUSIONS: Intravenous EMP was administered safely with paclitaxel and carboplatin and produced clinical outcomes similar to the outcomes achieved with the TEC regimen. Substitution of i.v. EMP for the oral formulation was found to result in a lower incidence of severe nausea but increased hepatic toxicity.     

Intestinal permeability,vitamin A absorption,alpha-tocopherol,and neopterin in patients with rectal carcinoma treated with chemoradiation

Although gastrointestinal toxicity is one of the most common side effects of anticancer therapy, the diagnosis and assessment of this toxicity still depend mostly on anamnestic data. Measurement of intestinal permeability is one of potential methods of non-invasive laboratory evaluation of gastrointestinal toxicity. The aim of the present study was to investigate intestinal permeability, vitamin A absorption, serum alpha-tocopherol, and urinary neopterin in patients with rectal carcinoma treated with chemoradiation. We have studied intestinal permeability, vitamin A absorption, serum alpha-tocopherol, and urinary neopterin in 17 patients with rectal carcinoma treated with chemoradiation. Urinary lactulose, mannitol, and xylose were measured by capillary gas chromatography, and serum alpha-tocopherol, retinol, retinyl esters, and urinary neopterin were determined by high-performance liquid chromatography. Lactulose/mannitol ratio was increased 5 and 6 weeks after the start of the treatment. Serum alpha-tocopherol was decreased significantly throughout the course of treatment, but no significant changes were observed in postprandial serum concentrations of retinyl esters or in the concentrations of urinary neopterin. A correlation was observed between baseline parameters of intestinal permeability and urinary neopterin. The measurement of intestinal permeability using the lactulose/mannitol test may represent a sensitive tool in the detection of changes associated with chemoradiation in patients with rectal carcinoma. The therapy is also associated with a decrease of alpha-tocopherol.     

Combination chemotherapy with adriamycin, cyclophosphamide, vincristine, prednisolone (VEPA) in non-Hodgkin's lymphoma, with special reference to correlation of surface phenotype with response and survival

Thirty-seven previously untreated patients with advanced non-Hodgkin's lymphoma were treated with VEPA therapy. The complete remission (CR) rate was higher in the patients with diffuse B-cell lymphoma (75%) than in those with follicular B-cell lymphoma (20%) and T-cell lymphoma (42%). Two characteristics, i.e., elevated LDH and bone marrow involvement, were negatively associated with response rate in patients with diffuse lymphoma (B-, T-). The median duration of CR has not yet been reached, and the 2-year relapse-free rate was 64% for cases of diffuse B-cell lymphoma, while for T-cell lymphoma patients, the median duration of CR was 7 months. For diffuse B-cell lymphoma patients, the median survival has not yet been reached, and the 2-year survival rate was 57%. On the other hand, median survival for T-cell lymphoma patients was 12 months. VEPA therapy was less effective for the treatment of T-cell lymphoma, and a more intensive regimen should therefore be designed to overcome the potential aggressiveness of T-cell lymphoma.     

Results with chemotherapy comprised of cyclophosphamide, doxorubicin, vincristine, and prednisone followed by radiotherapy with or without prechemotherapy surgical debulking for patients with bulky, aggressive lymphoma

BACKGROUND: The authors performed a case-control analysis of local control, progression free survival, and overall survival in patients with Stage I-II aggressive lymphomas measuring > or = 7 cm in greatest dimension who were treated initially with or without surgical debulking: All patients then received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) based chemotherapy followed by involved field radiotherapy. METHODS: From May 1975 through May 1996, 50 patients were treated with (n = 25 patients) or without (n = 25 patients) resection of > 80% of their bulky lymphomas. Chemotherapy consisted of 3-12 cycles of CHOP. In general, patients who underwent debulking received three cycles of chemotherapy, whereas patients who did not undergo debulking received at least six cycles of chemotherapy. The total radiotherapy dose was 40.8 grays (Gy) +/- 4.2 Gy (mean +/- standard deviation). RESULTS: The median follow-up was 62 months. Patients who underwent debulking were similar prognostically to patients who did not. There was a trend toward improved local control (5 year rates: 96% vs. 80%; P = 0.10) and overall survival (5 year rates: 83% vs. 71%; P = 0.18) in patients who underwent debulking compared with patients who did not, respectively. Progression free survival was significantly better for patients who underwent debulking compared with patients who did not (5 year rates: 88% vs. 62%, respectively; P = 0.04). CONCLUSIONS: Because this study was retrospective, selection bias may account for the observed difference in progression free survival. Because it is unlikely that a trial randomizing patients with bulky, aggressive lymphoma to surgery will be conducted, the authors' current efforts are focused on escalation of the total radiotherapy dose as a possibly less costly and less morbid approach toward improving progression free survival for these patients.