A role of BPTF in viral oncogenicity delineated through studies of heritable Kaposi sarcoma.

Kaposi sarcoma (KS), caused by Herpesvirus-8 (HHV-8; KSHV), shows sporadic, endemic, and epidemic forms. While familial clustering of KS was previously recorded, the molecular basis of hereditary predilection to KS remains largely unknown. We demonstrate through genetic studies that a dominantly inherited missense mutation in BPTF segregates with a phenotype of classical KS in multiple immunocompetent individuals in two families. Using an rKSHV.219-infected CRISPR/cas9-model, we show that BPTFI2012T mutant cells exhibit higher latent-to-lytic ratio, decreased virion production, increased LANA staining, and latent phenotype in viral transcriptomics. RNA-sequencing demonstrated that KSHV infection dysregulated oncogenic-like response and P53 pathways, MAPK cascade, and blood vessel development pathways, consistent with KS. BPTFI2012T also enriched pathways of viral genome regulation and replication, immune response, and chemotaxis, including downregulation of IFI16, SHFL HLAs, TGFB1, and HSPA5, all previously associated with KSHV infection and tumorigenesis. Many of the differentially expressed genes are regulated by Rel-NF-κB, which regulates immune processes, cell survival, and proliferation and is pivotal to oncogenesis. We thus demonstrate BPTF mutation-mediated monogenic hereditary predilection of KSHV virus-induced oncogenesis, and suggest BPTF as a drug target.

Perspectives of cancer patients during the COVID-19 outbreak in Israel: The long-term implications on support and well-being in an exploratory qualitative study.

OBJECTIVES: The COVID-19 pandemic's ongoing effects and long-term implications for the mental and social state of cancer patients are not yet fully known. The current study examined cancer patients' feelings about the pandemic's long-term impact on daily life 1 year after its outbreak in Israel and after the patient's vaccination against the virus. METHODS: Ten in-depth semi-structured interviews were conducted with cancer patients between February and April 2021. RESULTS AND CONCLUSIONS: Findings indicated four main themes: (1) managing medical care and support from the medical staff, (2) the effect of the pandemic on social interactions; (3) the impact of the pandemic on family and social support and (4) the patients' psychological well-being. Despite the patients being vaccinated, the full impact of the pandemic on cancer patients' mental and social states is still fully apparent. The findings reflect the need to assess and monitor the patients' mental state and social and medical needs during this complex time and the importance of developing external support networks.

[PRIMARY GASTRIC PLASMACYTOMA IN A BREAST CANCER MALE PATIENT].

INTRODUCTION: Plasmacytoma is a malignant tumor of the plasma cells. Extra-medullary plasmacytoma is rare and with an even lower incidence appears as a primary tumor of the stomach. Initial onset of the disease in the upper gastrointestinal tract is reported in the literature as just second to primary plasmacytomas of the head and neck system. The presenting symptoms are related to the organ involved and systemic symptoms can be weight loss, pain, bleeding and even fever. As this is a rare disease, there is no standard treatment and patients undergo endoscopic resection or chemotherapy with or without additional radiation. The prognosis of the disease depends on the possible future diagnosis of multiple myeloma which can be up to 50% within only a few years. We hereby report a case of a male patient with a past locally advanced breast cancer who was on prolonged adjuvant hormonal treatment. He developed a new symptom of melena and underwent a thorough evaluation including imaging and repeated biopsies from a large gastric lesion. The results were inconclusive mainly because of the differential diagnosis between breast cancer metastases and a new second primary malignancy. In view of a clinical deterioration and lack of diagnosis, an operation of radical gastrectomy was eventually performed only to surprisingly diagnose a rare hematologic disease of the stomach - gastric plasmacytoma. This diagnosis is rare in itself, especially having his previous male breast cancer and maternal multiple myeloma. The diagnostic procedure in this case had also provided the full treatment for his illness.

Oncology Treatments during the COVID-19 Pandemic in Israel: the ONCOR Study.

BACKGROUND: The increased susceptibility of cancer patients to coronavirus disease-2019 (COVID-19) infections and complications calls for special precautions while treating cancer patients during COVID-19 pandemics. Thus, oncology departments have had to implement a wide array of prevention measures. OBJECTIVES: To address issues associated with cancer care during the COVID-19 pandemic and to assess the implementation of measures aimed at containment of COVID-19 diffusion while allowing continuation of quality cancer care. METHODS: A national survey among oncology departments in Israel was conducted between 12 April 2020 and 14 April 2020. Eighteen heads of hospital-based oncology departments completed a self-report questionnaire regarding their institute's preparedness for treatment of cancer patients during the COVID-19 pandemic. RESULTS: In this national survey, prevention measures against COVID-19 spread were taken prior to patients' arrival and at arrival or while staying in the departments. Most participants (78-89%) reported using a quick triage of patients and caregivers prior to their entrance to the oncology units, limiting the entrance of caregivers, and reducing unnecessary visits to the clinic. Switching to oral therapies rather than intravenous ones when possible was considered by 82% and shortage in personal protective equipment was reported by five (28%) heads of oncology departments. Some differences between large and small/medium sized medical centers were observed regarding issues related to COVID-19 containment measures and changes in treatment. CONCLUSIONS: Oncology departments in Israel were able to prepare and adapt their services to guidelines and requirements related to the COVID-19 pandemic with little harm to their treatment capacity.

Treatment of cervix carcinoma FIGO IIIb with Photofrin II as a radiosensitizer: a case report.

Cervical cancer is the fourth-most common type of cancer and cause of death in women. Human papilloma virus (HPV) infection is responsible for over 90% of cervical cancers. The recommended treatment is multidisciplinary, consisting of a combination of surgery, chemotherapy, and radiation therapy. The standard treatment in advanced stages, such as FIGO IIIb, is radio-chemotherapy with overall 5-year survival of 32%. Photofrin II has been demonstrated to serve as a specific and selective radiosensitizing agent in both in vitro and in vivo tumor models, admitted for radiation therapy. We describe a patient with advanced cervical carcinoma (squamous cell) who contacted us for further therapy in 2003. Staging included a gynecological examination, colonoscopy, explorative laparotomy, biopsy and pelvic MRI. The explorative laparotomy showed enlarged pelvic and para-aortal lymph nodes. The histologic examination described tumor infiltrated, positive lymph nodes (Stage FIGO IIIb). Contrary to recommendations, the patient refused standard treatment with a combination of chemotherapy and radiotherapy, but accepted a combined treatment of Photofrin II as a radiosensitizer and a radiotherapy procedure. She underwent irradiation with a 50.4 + 14 Gy boost with fractionation of 1.8 Gy day-1 for 5 days per week; the boost was given with 2 Gy fractions. She was injected with a single intravenous dose in a slow infusion (30 min) of 1 mg kg-1 of Photofrin II 24 h prior to radiation therapy. A localized relapse in the cervix appeared after 30 months, and was resected by hysterectomy. The patient is still alive with no evidence of disease after 15 years.

The combination of gemcitabine and carboplatin shows similar efficacy in the treatment of platinum-resistant and platinum-sensitive recurrent epithelial ovarian cancer patients.

The aim of this study was to evaluate progression-free survival, overall survival (OS), response rate (RR), and clinical benefit in recurrent ovarian cancer patients treated with gemcitabine and carboplatin and to compare the outcome among platinum-resistant and platinum-sensitive patients. A retrospective study using the medical records of patients diagnosed and treated for recurrent epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma with gemcitabine and carboplatin from 2005 through 2012 at the Tel Aviv Sourasky Medical Center. The treatment regimen was carboplatin (area under the curve=5) administered on day 1 and gemcitabine 850 mg/m administered on days 1 and 8 in a 21-day cycle. Seventy patients with a median age of 57 years (range: 38-86) were included in the study. Most patients (94.3%) were initially diagnosed with stage III-IV disease and 44.3% had platinum-sensitive disease. Median progression-free survival in platinum-sensitive patients was 6.3 months [95% confidence interval (CI): 4.3-8.3] and 6.3 months (95% CI: 4.6-7.9) in platinum-resistant patients. Median overall survival was 15.8 months (95% CI: 13.6-18.1) in the platinum-sensitive patients and 18.4 months (95% CI: 10.0-27.8) in the platinum-resistant patients. Platinum-sensitive patients had a RR of 43.2% and platinum-resistant patients had a RR of 39.1%. The clinical benefit was 70.5% in platinum-sensitive patients and 65.2% in platinum-resistant patients. Overall treatment had a favorable safety profile. Gemcitabine and carboplatin demonstrate moderate toxicity with similar efficacy in both platinum-sensitive and platinum-resistant epithelial ovarian cancer, suggesting reversal of platinum resistance by gemcitabine.

The Role of Nurses in the Quality of Cancer Care Management: Perceptions of Cancer Survivors and Oncology Teams.

OBJECTIVES: This study aimed to explore the perceptions of cancer survivors and oncology professionals of quality in cancer care and the role of oncology nurses in prompting and maintaining quality across the cancer care continuum. DATA SOURCES: Semistructured in-depth interviews were conducted with 16 cancer survivors and 22 healthcare professionals between August and October 2021. The interviews were transcribed and analyzed using ATLAS.ti v8 software according to a thematic analysis method based on grounded theory. The COnsolidated criteria for REporting Qualitative research (COREQ) was used to guide the report of the study. CONCLUSION: Four main themes emerged from the interviews, which are outlined as follows. (1) Patient participation in the cancer care plan: shared information and decision-making; (2) emotional and support aspects in cancer care; (3) continuity in cancer care: from being a patient at the hospital to a survivor in the community; and (4) cancer care management. Cancer survivors pointed to elements that can increase the quality of cancer care, including the ongoing provision of information, support in decision-making, and continuity of care. Oncology staff interviewees mentioned the need for a single staff member to manage the cancer care plan and serve as a case manager for patients and survivors. IMPLICATIONS FOR NURSING PRACTICE: Nurses have a central role in achieving the highest possible quality of cancer care for the growing number of survivors and their families. It is recommended to expand the role of oncology nurses, providing them the training and competencies needed to formally declare them as care managers throughout the continuum of cancer care.

Nurses and Physicians' Perceptions Regarding the Role of Oncology Clinical Nurse Specialists in an Exploratory Qualitative Study.

The purpose of the study was to examine the attitudes of nursing and medical teams about the role of oncology clinical nurse specialists in the healthcare system in Israel, where, unlike many countries in the world, such a role has not yet been developed or professionally defined. We conducted 24 interviews with physicians and nurses between August and October 2021. The interviews were transcribed and analyzed using a thematic analysis method. The Consolidated Criteria for Reporting Qualitative Research checklist was used to report the study. Five main themes emerged from the interviews: (1) contribution to the healthcare system, (2) contribution to the patient, (3) drawing professional boundaries, (4) additional responsibilities and authority for oncology clinical nurse specialists, and (5) the field's readiness for a new position of oncology clinical nurse specialists. The findings provide evidence about the need to develop the role of clinical nurse specialists in the oncology field due to its potential benefits for nurses, physicians, patients, family members, and the healthcare system. At the same time, an in-depth exploration of the boundaries of the role and its implementation, in full cooperation with the oncologists and relevant professional unions, is needed to prevent unnecessary conflicts in the oncology field. Professional development training programs in nursing must create a platform for open dialogue between key stakeholders, nurses, and physicians, in order to help all involved parties, place the benefits to the patients above any personal or status considerations.

The Oncology Clinical Nurse Specialist: A Rapid Review of Implementation Models and Barriers around the World.

The role of a clinical nurse specialist in oncology varies greatly between healthcare systems, and implementing this healthcare role with its multifaceted and co-existing responsibilities may prove challenging. While already integrated into healthcare systems and services in several European countries, Asia, Canada, and the United States, other countries are just beginning to develop clinical nursing specialties. The current study aims to provide healthcare policymakers with up-to-date evidence that focuses on the diverse modes of oncology clinical nurse specialist role implementation across several healthcare systems and pertinent implementation challenges as described in the literature. A rapid evidence assessment was carried out in order to provide policymakers with a rigorous review in a condensed timescale. Initially, only items in the English language were included, and "grey literature" was excluded. We searched PubMed between 1 January 2022 and 28 February 2022 and two independent scholars reviewed items. Based on 64 papers, both non-scientific and papers that met the initial criteria of the rapid review, we describe the modes of implementation of the oncology clinical nurse specialist in the United States, Canada, United Kingdom, Japan, Brazil and Australia. Barriers to implementation include conflicts around role boundaries, skepticism and lack of organizational support, as well as fears that oncology clinical nurse specialists will "encroach" on doctors' powers. In contrast, an oncology clinical nurse specialist is found to be universally more accessible to patients and their families and can help physicians deal with difficult workloads, among other advantages. Conclusions: This role offers a myriad of gains for cancer patients, oncology physicians, and the healthcare system. The literature demonstrates that it is a necessary role, albeit one that brings specific implementation challenges.

Patients' and oncologists' perceptions towards the discussion on high-cost innovative cancer therapies: findings from a qualitative study.

OBJECTIVES: In the last decades, innovative technologies for cancer treatment were developed rapidly. In most cases, their price is high, with no funding offered by public health systems. The present study examined the perceptions of oncologists, patients and family members regarding the challenges in discussing innovative cancer treatments. DESIGN: Qualitative study, using in-depth semistructured interviews. Interviews examined public versus private financing, therapist-patient-family discourse, modes of decision making and implications on health policy and inequalities. PARTICIPANTS: Sixteen cancer patients, six family members of cancer patients and 16 oncologists participated in the study. RESULTS: Four themes emerged from data analysis: the economic consideration in the decision on cancer treatment, the options of funding high-cost private treatments, psychosocial aspects of the discussion on treatment costs and health policy in oncology and its social aspects. CONCLUSIONS: Findings emphasise the importance of considering costs when recommending expensive care and addressing the emotional element of innovative treatment, as most patients expect. The findings present various psychosocial aspects taking part in the complicated decision to use unfunded cancer treatment and its broad implications, which may use as a basis for developing a guided framework for oncologist-patient discourse.

Health locus of control in cancer patient and oncologist decision-making: An exploratory qualitative study.

OBJECTIVE: To investigate how cancer patients' and family members' perspective and health locus of control are presented in clinical encounter decision-making. METHODS: Semi-structured in-depth interviews were carried out with 16 cancer patients and 6 family members living in Israel (n = 22). Interviews were transcribed verbatim, and data were analyzed using thematic analysis. RESULTS: Following the health locus of control model, the findings were divided into an external and internal locus of control themes, and we added a theme regarding shared decision-making. Internal locus of control sub-themes included asking for a second opinion, negotiating with the doctor, asking questions, looking for information, and fighting for their rights. External locus of control sub-themes included powerful others, oncologists, and fate. The dominant approach of most of the interviewees was an external locus of control. Women demonstrated more external locus of control than men. On the direct question of who should decide on treatment-the doctor, the patient, or both jointly-the answers ranged from only the doctor (n = 8) to together (n = 7) to only the patient (n = 8). CONCLUSIONS: This study provides insights into different aspects of locus of control in the clinical encounter involving cancer patients. The findings reflect the need to devote comprehensive attention to cancer patients' perceptions and experiences in the clinical encounter. A patient-centered care approach and a personalized framework for decision-making in cancer care are essential to achieving better treatment outcomes. Further research can engage in the development and validation of an up-to-date health locus of control questionnaire for cancer patients based on the findings of this study.

Pembrolizumab as a first line therapy in a patient with extensive mucoepidermoid salivary gland carcinoma. A complete clinical, radiological and pathological response. A very specific case.

BACKGROUND: Patients with advanced salivary gland malignancies (SGCs) have few therapy options. Although results from newly published trials suggest that checkpoint inhibition may be useful in a subgroup of patients, there are no clear criteria for PD-L1 score in SGCs. Chemotherapy benefits were observed to be limited, with a dismal prognosis in unresectable and high-grade SGC. Immunotherapies have demonstrated extraordinary efficacy in a variety of cancers, including non-small cell lung cancer and malignant melanoma. Anti-PD-1 antibody pembrolizumab has been shown to have potent anti-tumor action in a number of clinical trials. CASE PRESENTATION: We report a unique case of advanced high grade mucoepidermoid carcinoma of the parotid salivary gland after Pembrolizumab treatment as a first line therapy. The tumor was downstaged as a result of the pembrolizumab treatment, allowing for a successful surgical excision with no facial nerve sacrifice and no major neoadjuvant treatment adverse effects, and the final specimen pathology was tumor-free. In these types of malignancies, a similar technique resulted in a complete response (CR) radiologically and pathologically has never been discussed before. CONCLUSIONS: In pretreated patients with high-grade salivary gland mucoepidermoid carcinoma, pembrolizumab showed good anticancer activity and provided a clinically, radiologically, and pathological response with a viable treatment choice. More research is needed to bring Pembrolizumab to the front-line of treatment. The time and duration of medication should be compared to the time required for surgery in these investigations.

Recommending Unfunded Innovative Cancer Therapies: Ethical vs. Clinical Perspectives among Oncologists on a Public Healthcare System-A Mixed-Methods Study.

Over the past decade, there has been a growing development of innovative technologies to treat cancer. Many of these technologies are expensive and not funded by health funds. The present study examined physicians' perceptions of the ethical and clinical aspects of the recommendation and use of unfunded technologies for cancer treatment. This mixed-methods study surveyed 127 oncologists regarding their perceptions toward using unfunded innovative cancer treatment technologies, followed by in-depth interviews with 16 oncologists. Most respondents believed that patients should be offered all treatment alternatives, regardless of their financial situation. However, 59% indicated that they often face dilemmas regarding recommending new unfunded treatments to patients with financial difficulties and without private health insurance. Over a third (38%) stated that they felt uncomfortable discussing the cost of treatment with patients. A predictive model found that physicians facing patients whose medical condition worsened due to an inability to access new treatments, and who expressed the opinion that physicians can assist in locating funding for patients who cannot afford treatments, were more likely to recommend unfunded innovative therapies to patients (F = 5.22, R2 = 0.15, p < 0.001). Subsequent in-depth interviews revealed four key themes: economic considerations in choosing therapy, patient-physician communication, the public healthcare fund, and discussion of treatment costs. Physicians feel a professional commitment to offer patients the best medical care and a moral duty to discuss costs and minimize patients' financial difficulty. There is a need for careful and balanced use of innovative life-prolonging technologies while putting patients at the center of discourse on this complex and controversial issue. It is essential to develop a psychosocial support program for physicians and patients dealing with ethical and psychosocial dilemmas and to set guidelines for oncologists to conduct a comprehensive and collaborative physician-patient discourse regarding all aspects of treatment.

The Organizational Atmosphere in Israeli Hospital during COVID-19: Concerns, Perceptions, and Burnout.

The COVID-19 crisis poses challenges to healthcare systems and requires micro- and macro-organizational adaptations. This study examined the organizational atmosphere in Israeli hospitals by evaluating workers' perceptions and concerns about the COVID-19 crisis and its management. At the end of the pandemic's first wave in Israel, 547 healthcare workers responded to an online survey, which inquired about COVID-19 concerns at the individual and family level, perceptions at the national and organizational level, perceptions of the way the crisis was managed, self-assessment of coping with the crisis and burnout, and demographics. Findings showed that healthcare workers expressed deep concerns for family members and apprehension at a national level. Respondents noted that they were coping well with the crisis while expressing negative perceptions of how the crisis was managed. A regression model showed that the low self-assessment of medical staff of coping with the crisis, deep concerns at the organizational level, negative perceptions of crisis management, and providing care for COVID-19 patients were predictors of burnout. The findings emphasize the importance of developing a supportive organizational culture for hospital workers. Awareness of their concerns and perceptions is essential to improve organizational culture and healthcare systems' ability to continue fighting the virus and confront future health crises.

Erratum: Goblet cell carcinoid of the appendix: Two case reports and a review of the literature.

[This corrects the article DOI: 10.3892/mco.2019.1921.].

Ondansetron for the prevention of seasickness in susceptible sailors: an evaluation at sea.

BACKGROUND: Seasickness is a common problem, causing a significant decrement in performance among naval crew. In about 20-60% of crewmembers, symptoms appear with varying intensity depending on the sea state and the duration of the voyage. Recent studies have suggested antiemetic 5HT3 blockers as a possible treatment for motion sickness, emphasizing their minor clinical and cognitive side effects. The purpose of the present study was to evaluate the 5HT3 blocker ondansetron in the prevention of seasickness. METHODS: There were 16 volunteers with a normal otoneurologic examination and no previous medical history of inner ear disease or vertigo who took part in a double blind, randomized, crossover study. During an initial learning phase, the participants practiced on a battery of computerized performance tests until their results stabilized. Ondansetron 8 mg or placebo was administered 2 h before sailing aboard a 500-ton naval vessel in mild sea conditions. Participants did the performance tests and completed a questionnaire evaluating their seasickness symptoms 4 h into the voyage. RESULTS: No statistically significant reduction of seasickness symptoms was demonstrated between ondansetron treatment and placebo (a Wiker score of 2.69 +/- 1.78 and 2.81 +/- 1.97, respectively). There was no statistically significant difference in side effects or the results of the performance tests. CONCLUSION: In this study, ondansetron was not found to be beneficial in the treatment of seasickness. It could be speculated that the mechanism of nausea in seasickness is different from that of toxin-induced nausea.

Management of Peripheral Neuropathy Induced by Chemotherapy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is considered a severe side effect of therapeutic agents with limited treatment options. The incidence of CIPN in cancer patients is approximately 3-7% in cytostatic monotherapy and as high as 38% in cases of polychemotherapy. The prevalence of CIPN was found to be 68% within the first month of chemotherapy treatment. In some cases, CIPN can resolve, partially or completely, after completion of the treatment; in other cases, it can remain for a long time and affect the patient's quality of life. OBJECTIVE: The aim of this study is to present up-to-date data regarding available treatment options for the management of CIPN. MATERIALS AND METHODS: The up-to-date guidelines of ESMO (European Society for Medical Oncology), ASCO (American Society of Clinical Oncology), ONS (Oncology Nursing Society), NCI (National Cancer Institute), and NCCN (National Comprehensive Cancer Network) were reviewed and included in the manuscript. RESULTS: The use of tricyclic antidepressant (TCA), selective serotonin norepinephrine reuptake inhibitor (SSNRI), pregabalin, and gabapentin are recommended as first-line treatment. Other treatment options were offered as second and third lines of treatment (lidocaine patches, capsaicin high-concentration patches, tramadol, and strong opioids, respectively); however, lower significance was demonstrated. Inconclusive results were found in the use of cannabinoids, drug combinations, antiepileptics, antidepressants, and topical drugs. CONCLUSION: TCA, other antidepressants, and opioids could be recommended as treatment. Yet, we could not recommend an ideal therapeutic agent for the prevention or treatment of CIPN. Therefore, CIPN continues to be a challenge to clinicians and our patients.

Goblet cell carcinoid of the appendix: Two case reports and a review of the literature.

Goblet cell carcinoid or carcinoma (GCC) is a rare tumor found incidentally during routine management of acute appendicitis. GCCs are more aggressive compared with conventional appendiceal tumors but less aggressive compared with adenocarcinomas, and they often present with serosal and mesoappendiceal involvement. We herein report two cases of acute appendicitis in a 45-year-old female and a 60-year-old male with varied clinical symptoms. Pathological examination of the appendix revealed the presence of adenocarcinoma with goblet cells and a Ki-67 index of 25% (grade 3) and 15% (grade 2), respectively. Subsequent right hemicolectomy was performed according to the current guidelines. No signs of disease recurrence or metastasis were detected during regular follow-up. However, the lack of a standardized classification system for GCC and the discrepancies in specific reliable markers renders their prognostic and predictive value in GCC at diagnosis insufficient. The present study also aimed to address current concerns regarding the diagnosis, treatment and prognosis of GCC, as well as the need to review and update current guidelines. To conclude, proper clinical management and the prediction of outcome for patients with GCC varies according to the classifications or staging criteria used by the clinicians; hence, a review of the current guidelines should be considered.

Glioblastoma Multiforme, Diagnosis and Treatment; Recent Literature Review.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, with an incidence of 3.19 cases per 100,000 person years and remarkably poor prognosis showing a 5-year survival rate of 4-5%, and only a 26-33% survival rate at 2 years in clinical trials. OBJECTIVE: In this paper, we review the different types of treatment modalities based on the relevant databases. Methods of diagnosis will be described briefly. METHOD: Systemic compilation of the relevant literature. RESULTS & CONCLUSION: Today's treatments cannot cure GBM patients but only extend their overall survival. The use of chemoradiation, immunotherapy, and radio sensitizers as an adjuvant therapy cannot reduce the high rates of recurrence within a few months after treatment. Radiotherapy will remain the backbone of the treatment but new treatment modalities must be developed.

A biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, temozolomide (Temodal), interferon-alfa and interleukin-2 for metastatic melanoma: a phase II study.

Our objective was to evaluate the toxicity and antitumor efficacy of concurrent biochemotherapy in metastatic melanoma patients and the effectiveness of adding temozolomide to protect the brain from metastases. Twenty-three patients with advanced inoperable melanoma were hospitalized for 5-6 days for the following treatment: cisplatin 20 mg/m daily for 4 days, vinblastine 1.6 mg/m daily for 4 days and oral temozolomide 250 mg/m daily for 5 days, with 18 x 10 IU/m intravenous interleukin-2 by continuous infusion for 4 days (the dose was cut daily by 50%) and 5 x 10 U/m interferon-alfa subcutaneously daily for 5 days, repeated at 28-day intervals for a maximum of nine courses. According to the standard World Health Organization response criterion, the objective response rate was 43.4% and the median survival was 18.6 months. All but one patient survived for more than 12 months, and no responding patient progressed first in the brain. Substituting dacarbazine by temozolomide in the MD Anderson melanoma section protocol appears to offer protection against dissemination of brain metastases, equal activity in the periphery and a possible lower incidence of toxicity due to the oral route.