Clinical outcome of adjuvant endocrine treatment according to Her-2/neu status in breast cancer.

Background & objectives: An association between over-expression of proto-oncogene Her-2/neu and resistance to tamoxifen in estrogen receptor (ER) positive, primary and metastatic breast cancer has been suggested. HR+/Her-2/neu+ patients have a poor response to endocrine therapy, making this group a matter of debate. The present study was carried out to examin whether Her-2/neu expression in breast cancer patients predicted tamoxifen effectiveness. Methods: An enzyme-linked immunosorbent assay (ELISA) specific for the extracellular domain of the Her-2/neuoncoprotein product was used to detect serum Her-2/neu levels in 207 patients with histological confirmed breast cancer. Tissue Her-2/neu expression was studied in 100 breast cancer patients by immunohistochemistry (IHC) and compared with serum Her-2/neu levels by ELISA. Results: Among 207 histologically confirmed breast cancer patients, 53 were serum Her-2/neu positive. Patients who were treated with surgery, chemotherapy, and radiotherapy showed significantly (P<0.05) reduced serum Her-2/neu levels, showing good response to treatment. Patients who were treated with tamoxifen in addition to the above regimen did not show any significant reduction in serum Her-2/neu levels showing resistance to treatment. Interpretation & conclusions: The present findings study support the hypothesis that Her-2/neu overexpression contributes to tamoxifen resistance. Trastuzumab or other growth factor inhibitors should be used in combination with tamoxifen, since monotherapy is not likely to be optimal in HR+/Her-2/neu+ tumours.

Bone metastasis in hepatocellular carcinoma: need for reappraisal of treatment.

Bone is an uncommon site of metastasis in patients with hepatocellular carcinoma (HCC), and often overlooked. We report two cases that had isolated bone metastasis; one of them had prolonged disease-free survival. The present series, along with the literature review, reinforces the idea that HCC should be considered in the differential diagnoses in patients presenting with metastases in bone. The presence of isolated bone metastases need not necessarily indicate poor prognosis, and all such patients need to be offered chemotherapy and at least one of the bone-directed therapies (either local radiation in cases of localized disease or bisphosphonates in the presence of extensive disease) as they may have a better outcome with therapy.

Treatment outcome and cost-effectiveness analysis of two chemotherapeutic regimens (BEP vs. VIP) for poor-prognosis metastatic germ cell tumors.

BACKGROUND: In patients with small-volume disseminated disease of germ cell tumors, cure can be achieved with four cycles of bleomycin, etoposide, and cisplatin (BEP). However, around 20% of these cases are not curable. Strategies to improve cure rates have shown that none of the currently available modalities were superior to the others. Among the most used ones, BEP and VIP (etoposide, cisplatin, and ifosfamide) have been the most studied. However, there are no reports comparing the two, except for a few in abstract forms from southern India. Therefore, we did a treatment outcome and cost-effectiveness analysis of two chemotherapeutic regimens (BEP vs VIP) that are used in poor-prognosis metastatic germ cell tumors. MATERIALS AND METHODS: All male patients with germ cell tumors, diagnosed as having poor risk by IGCCCG, between January 2002 and December 2004 were included in the study. Clinical, laboratory, and other data were recorded. The patients were stratified into two categories on the basis of the type of chemotherapeutic regimen they received. RESULTS: In all, 46 patients were analyzed, with a median follow up of 26.6 months. The baseline characteristics (age, stage, PS, histology, and serum markers) were not different in the two treatment arms. There is no significant difference in the outcome with either of the chemotherapeutic modalities. VIP is less cost effective and more toxic compared to BEP. CONCLUSION: In view of the greater toxicity and cost of therapy, as well as lack of either overall or disease free survival advantage, VIP is not a preferred option for patients with high-risk germ cell tumors in the Indian setting and it is still advisable to treat patients with BEP.

Clinical utility of serum human epidermal receptor-2/neu detection in breast cancer patients.

BACKGROUND & OBJECTIVE: In breast cancer, the HER-2/neu gene is amplified in 20-30 per cent of cases. The mechanism by which the amplification/overexpression occurs is not known. Elevated serum HER-2/neu levels have been shown to be associated with a poor clinical prognosis and decreased survival in early stage breast cancer patients, and thus might help in management of the disease. The present study was therefore to estimate the serum HER-2/neu levels in breast cancer patients and associate with other prognostic factors. METHODS: Serum HER-2/neu levels were studied in 207 patients with cancer breast, 15 benign breast diseases (BBD) and 175 age-matched healthy controls. Patients' age, menopausal status, node and hormone receptor status were compared with serum HER-2/neu levels. RESULTS: Serum HER-2/neu overexpression was associated with age, disease stage and positive nodal status but not with menopausal status. Serum HER-2/neu levels were negatively related with hormone receptor positivity. INTERPRETATION & CONCLUSION: HER-2/neu serum test could be done more frequently in women with breast cancer irrespective of the hormone receptor status, to suggest modifications in systemic adjuvant therapy, including possibly the use of Herceptin.

Unusual metastasis in colorectal cancer.

Metastasis from colorectal carcinoma occurs by either lymphatic or hematogenous spread. The most common sites of colorectal metastasis are the liver and lung. Involvement of the skin, muscles and bones are quite rare. The prognosis in such patients is usually poor. Herewith, we are reporting a case of colonic carcinoma who had cutaneous metastasis, muscular involvement and diffuse skeletal metastasis. At the end, she had brain metastasis, but liver and lung involvement was not observed till the end.

Safety and efficacy of an indigenous recombinant interferon-alpha-2b in patients with chronic myelogenous leukaemia: results of a multicentre trial from India.

BACKGROUND: Compared to hydroxyurea, treatment with interferon-alpha (IFN-alpha) is known to prolong survival in patients with chronic phase of chronic myelogenous leukaemia (CML) and was considered as first-line therapy till recently. We conducted a multicentre trial using an indigenous recombinant IFN-alpha-2b to evaluate its efficacy and toxicity in chronic phase CML. METHODS: Between September 2000 and August 2001, patients with chronic phase CML were recruited within 8 weeks of diagnosis at 7 centres in India. The study was approved by the Ethics Committee of each participating Institute and Informed, written consent was obtained from all patients. All patients were given the study drug in a dose of 5 million units daily subcutaneously. Response and survival analyses were done with intent-to-treat analysis. RESULTS: One hundred and fourteen patients (75 men and 39 women) were included in the study. Their ages ranged from 18 to 62 years (median 37 years). Fifty-seven per cent of patients had a haematological response; complete response in 31.6% and partial response in 25.4%. The median time to achieve complete haematological response was 6 months (range 3-12 months). Cytogenetic response was seen in 39.4% of patients; complete in 1.8%, partial in 28% and minimal in 9.6%. The median time to achieve partial and complete cytogenetic response was 6 and 12 months, respectively. Nineteen patients had progression (blast crisis n=15, accelerated phase n=4) while on treatment. Two patients refused further treatment after the initial 4 weeks due to IFN-a toxicity, mainly bone pains and fever. The major toxic effects of treatment were fever (78%), fatigue (25.4%) and myalgia (52%). No patient died of toxicity. Currently, 95 patients are alive, 91 in the chronic phase and 4 in the accelerated phase. Four patients were lost to follow up and all 15 patients with blast crisis died of progressive disease at a median Interval of 6.5 months (range 1-15 months). The Kaplan-Meier probability of survival at 36 months was 76%. CONCLUSION: This study confirms the efficacy of the indigenous recombinant IFN-alpha-2b in chronic phase CML. The drug has a toxicity profile similar to that of other preparations.

Waldenstrom's macroglobulinemia.

Waldenstrom's macroglobulinemia is an uncommon lymphoplasmacytic lymphoma presenting with hyperviscocity and autoimmune phenomenon. Disease is characterized by bone marrow infiltration by lymphoplasmacytic cells and raised IgM. Bone marrow morphology and immunohistochemistry is important for diagnosis. Course is indolent and anemia and age are most important prognostic factors. Treatment options include alkylating agents, anti-purine anti-metabolites, which though not curative but offer valuable responses. Newer agents like Rituximab and autologous transplant are being tried.

Chronic myeloid leukemia.

Chronic myeloid leukemia is one of the commonest hematological malignancies seen in clinical practice. It is the result of abnormal and excess cell proliferation due to de-regulated bcr-abl tyrosine kinase activity as a result of Philadelphia chromosome. The present article discusses the various options available to treat the disorder. Allogeneic stem cell transplant remains the gold standard and the only curative option. Hydroxyurea and Busulfan helps in controlling the total leukocyte count but fail to impact on survival. Interferon especially when combined with cytarabine is curative in minority of patients though a substantial number of patients achieve functional cure. Imatinib, a molecular targeted oral therapy, against bcr-abl tyrosine kinase is the latest addition to various treatment options. Early results appear very promising and can be considered as non- transplant standard of care.

Gastrointestinal stromal tumour--a paradigm shift in management of solid tumours.

Gastrointestinal stromal tumour (GIST) till recently were non-responsive to all chemotherapy agents. With the advent of c-kit, diagnosis of GIST has become more specific. STI-571, a tyrosine kinase, has become one of the first targeted therapeutic agent tobe active in solid tumour. At present it is the only agent with substantial activity in GIST.

Ewing's sarcoma with central nervous system metastasis--report of two cases.

Isolated central nervous metastasis is rare in patients with Ewing's sarcoma. Here we report two cases with CNS metastasis as the sole manifestation of relapse with a brief review of the literature.

Cardiac metastasis from carcinoma breast--a case report.

Secondary neoplasms of the heart are more common than primary tumours. Metastasis occurs most commonly from bronchogenic carcinoma followed by lymphoma and carcinoma breast. Most often cardiac metastasis go undetected as they are asymptomatic and occurs as a terminal event. A 51 year old lady who developed cardiac metastasis from carcinoma breast diagnosed during life is reported with brief review of the literature.