Serum and salivary sialic acid as a biomarker in oral potentially malignant disorders and oral cancer.

Background: Aberrant glycosylation is the universal feature of cancer and components of various glycoconjugates, such as sialic acid is found to rise in various malignancies. The objective of this study was to evaluate the serum and salivary sialic acid in oral potentially malignant disorders (OPMD) and oral cancer (OC) to investigate the possibility of using this as a diagnostic marker. Materials and Methods: The study included 85 subjects, who were grouped as control (30), OPMD patients (25), and oral cancer patients (30). Serum and unstimulated whole saliva was collected from subjects of all groups and sialic acid estimation was done using spectrophotometry. The results were tabulated and analyzed statistically. Results: The mean serum sialic acid levels in normal, OPMD, and oral cancer group were 7.515, 19.620, and 55.235 mg/dL, respectively, whereas the levels of salivary sialic acid were 1.5113, 2.3302, and 9.0304 mg/dL, respectively. A very highly significant rise (P < 0.005) in serum and salivary sialic acid was observed in the study subjects compared with that of the control. Conclusions: The present study showed a significant and gradual increase in serum and salivary sialic acid from control to oral potentially malignant disorders to oral cancer. From this study we can suggest that sialic acid can be used as a reliable biomarker. As this monosaccharide is observed in saliva in detectable quantity, saliva can be used as a diagnostic medium for screening and early detection of oral cancer.

Ifosfamide-based chemotherapy in locoregionally advanced nasopharyngeal cancer: evaluation of its role as neoadjuvant chemotherapy.

The use of Ifosfamide-based chemotherapy in primary nasopharyngeal carcinoma (NPC), in neoadjuvant settings [NACT] has not been sufficiently evaluated. We present here a retrospective analysis of 78 patients of untreated, locoregionally advanced NPC patients who received Ifosfamide-Cisplatin-based NACT at our institute from 1997 to 2004. Definitive treatment comprised radical radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) using weekly Cisplatin. Post-NACT, 92% patients had a partial response (PR) while 3% had a complete locoregional response (CR). The rates of CR increased to 87% after completion of definitive treatment. With follow up (38 months), 29% patients developed recurrent/persistent disease. The local and locoregional control rates at 5 years were 76% and 73%, respectively. The 5-year overall survival (OAS) was 80% and disease-free survival was 65%. Grade III or more neutropenia was seen in 15%. Results of Ifosfamide-Cisplatin combination as a NACT in advanced NPC have been quite encouraging and need to be exploited further.

In vitro chemosensitivity profile of oral squamous cell cancer and its correlation with clinical response to chemotherapy.

CONTEXT: Oral cancers represent a disparate group of tumors with diverse clinical behavior and chemosensitivity profile. Currently, it is difficult to predict whether a tumor will respond to chemotherapy and which drug(s) will achieve the maximum clinical response. AIMS: To study in vitro chemosensitivity profile of oral cancers and to correlate the in vitro chemosensitivity of oral cancer to clinical response to chemotherapy. SETTINGS AND DESIGN: Prospective study in a tertiary cancer care center. METHODS AND MATERIAL: We prospectively studied the chemosensitivity profile of 57 untreated, advanced, unresectable oral cancers to cisplatin, methotrexate, 5-fluorouracil and their combinations by using histoculture drug response assay (HDRA) and correlated them to the clinical response to chemotherapy. STATISTICAL ANALYSIS USED: Chi Square test. RESULTS: Biopsy samples were successfully histocultured in 52/57 (91%) cases. Of these 52 evaluable patients, 47 had primary gingivo-buccal cancers and five had tongue / floor of mouth cancers. Based on the assay, 27 (52%) tumors were sensitive to cisplatin, 27 (52%) to methotrexate, 24 (46%) to 5-fluorouracil, 38 (73%) to combination of cisplatin and methotrexate and 36 (69%) to combination of cisplatin and 5-fluorouracil. Of these, 31 patients with good performance status received two cycles of chemotherapy using one or more of these test drugs. There was a significant correlation (p=0.03) between the in vitro chemosensitivity and the clinical response. Negative predictive value of the test was 80%, positive predictive value-69%, sensitivity-79% and specificity -71%. The overall accuracy of the assay was 74%. CONCLUSIONS: We found HDRA to be a fairly good predictor of chemo-response of oral cancer.

Rituximab (anti-CD20 monoclonal antibody) in lymphoproliferative malignancies: Tata Memorial experience.

Rituximab has been used extensively in lymphoproliferative disorders. We evaluated the results of 64 consecutive patients treated between 2001 and 2004 at our institution. This included 54 males and 10 females. The median age was 54 years (range 17 to 85 years). One-fourth of patients were above 60 years. The histology was aggressive NHL in 35, indolent NHL in 22 and 7 cases were diagnosed as CLL. Among NHL, sixteen were in early stage (I/II) and the remaining forty-one were in advanced stage (III/IV) of disease. B symptoms were present in 47% of cases. A total of 33 were de novo cases and 31 were previously treated. Rituximab monotherapy was used in 17 cases. Rituximab was used in combination with chemotherapy in the other 47 cases. Infusional toxicity included anaphylaxis in one, hypotension in one and minor infusional reactions in four others. The patient who developed anaphylaxis required discontinuation of further Rituximab. Growth factors were used in 25 patients. Febrile neutropenia occurred in 19 patients. The overall RR (CR + PR) was 72%. One patient had stable disease and progressive disease was documented in 17 patients. A total of seven patients died, three due to progressive disease, three due to chemotherapy related toxicity and one due to an unrelated cause. We conclude that Rituximab is a valuable addition to the treatment armamentarium of lymphoproliferative disorders.

A phase II study of gemcitabine and cisplatin in patients with advanced hepatocellular carcinoma.

The primary objective of this study was to determine the response rates of a combination of gemcitabine and cisplatin in unresectable hepatocellular carcinoma (HCC) in Indian patients. The secondary objectives were to evaluate the toxicity, time to progressive disease and overall survival for this combination. Chemonaive patients with histopathologically proven, bidimensionally measurable, stage Ill or IV unresectable HCC were enrolled into this study. All the patients were required to have a Zubrod's performance status not greater than 2, should not have undergone prior radiotherapy and were required to have adequate major organ function. Patients received gemcitabine (1250 mg/m2 intravenously over 30 to 60 min) on days 1 and 8, and cisplatin (70 mg/m2 intravenously over 2 hours) on day land every 21 days. Response assessment was done by a Computed Tomography scan after every two cycles of chemotherapy. From May to December 1999, 30 patients were enrolled in the study; they were all eligible for efficacy and toxicity analysis. Six (20%) patients achieved a partial response and 13 (43%) patients demonstrated stable disease with 11 (37%) patients showing disease progression. The median time to progression was 18 weeks (range 1 to 74 weeks) and the median duration of response was 13 weeks (range 4 to 68 weeks). The 1-year survival rate was 27% and the median overall survival was 21 weeks (95% CI: 17 to 43 weeks). WHO grade 3 and 4 anemia was seen in 11 (37%) and 2 (7%) patients, respectively. Four (13%) patients each experienced grade 3 and 4 neutropenia and grade 3 and 4 thrombocytopenia was seen in 2 (7%) patients each. Major, non-hematologic toxicities were grade 4 elevated bilirubin levels and grade 3 oral toxicity, in 1 patient (3%) each. This regimen was well tolerated and did show activity in Indian patients with advanced unresectable HCC. There is a need to further evaluate this combination in order to define its role in the treatment of HCC.

Two- vs three-drug combination chemotherapy in advanced or recurrent head and neck cancer: a single institution experience of 361 patients.

Head and neck squamous cancer is a major concern in India. The proportion of advanced cases is significantly high, and these patients have dismal survival prospects despite aggressive therapy. Often surgical resection and/or radiotherapy are not feasible in these patients. Hence, we decided to explore the option of neoadjuvant chemotherapy using effective agents like ifosfamide and paclitaxel in combination with cisplatin in these patients. A total of 361 patients were evaluable at the end of study. Of these, 207 had received ifosfamide and cisplatin and 154 had received taxanes (paclitaxel or docetaxel) in addition to ifosfamide and cisplatin. The ifosfamide-cisplatin group had an overall response rate of 66.67% (CR, 16.42%; PR, 50.24%) and the median duration of response was 5.5 mo; whereas the group in which taxanes were added, showed an overall response rate of 73.37% (CR, 7.79%; PR, 65.58%) with a median duration of response of 10 mo. The toxicity in both the groups was acceptable and there was no mortality. We conclude that taxane-based combinations have a significant activity in advanced head and neck squamous cancer and warrant further studies.

Neoadjuvant chemotherapy with ifosfamide and cisplatin combination in advanced head and neck cancer: a retrospective analysis of 519 patients: a single institution experience.

Advanced head and neck cancer is a major therapeutic problem in India. Ifosfamide has shown significant activity as a single agent in head and neck squamous carcinoma. In this study, we present our experience with two cycles of ifosfamide and cisplatin in the neoadjuvant setting given to a total of 519 patients. The complete response rate was 20% and the overall response rate was 80%. The treatment was well tolerated, there was no need for dose reduction, and there were no life-threatening side effects. We feel that this high response rate is sufficient to warrant more studies using ifosfamide-based combinations in a neoadjuvant setting for squamous carcinoma of the head and neck.

Survival of childhood acute lymphoblastic leukemia: results of therapy at Tata Memorial Hospital, Bombay, India.

The purpose of this study was to analyze the outcome of patients who completed therapy for acute lymphoblastic leukemia (ALL) and to study the role of an aggressive induction regimen in preventing post therapy relapses. Four hundred and twenty-two patients with ALL who completed therapy during the period 1975-1991 were followed. Two hundred and sixty patients received the aggressive MCP 841 protocol and 162 patients received various other less aggressive treatment regimens. Patients were followed with periodic examination and complete blood counts. The incidence of post therapy relapse was 27% in the less aggressive protocols and 15% in the MCP 841 protocol (p = 0.001). An higher percentage of relapses was seen in males (p = 0.05) and 89% relapses occurred within two years of stopping therapy. The relapse rate after 5 years of cessation of therapy was 0.59%. In conclusion, aggressive induction therapy is the most crucial factor in predicting relapses following cessation of therapy in ALL patients. However, relapses are unlikely to occur five years post therapy.

Myelodysplastic syndrome. A clinical and pathological analysis of 88 patients.

Eighty eight patients with myelodysplastic syndromes were studied to determine the clinical and pathological features and the prognosis. All the patients had anemia. Neutropenia was seen in 44% and thrombocytopenia in 78% patients. The subtypes included refractory anemia in six, refractory anemia with ringed sideroblasts in three, refractory anemia with excess blasts in 30, refractory anemia with excess blasts in transformation in 32 and chronic myelomonocytic anemia in 17 patients. Forty four patients who received chemotherapy were evaluable for response. Three of the 15 patients treated with hydroxyurea achieved partial remission. Eighteen patients were treated with low dose cytosine arabinoside and complete remission was achieved in five and partial response in six patients. Aggressive chemotherapy was given to 11 patients at the onset of the illness resulting in complete remission in six and partial response in two patients. Nineteen of the 88 patients transformed to acute myeloid leukemia. The crude survival of all the patients ranged from 15 days to 22.5 months. The mortality was due to hemorrhage in 15% and septicemia in 85%. Our data reveals ineffectiveness of the current therapy and emphasizes on the need to develop newer therapeutic approaches.

Primary lymphoreticular tumors of the orbit.

Primary orbital lymphomas are rare. We report nine such cases (4 with DWDL, 3 with DPDL, 1 with DHL and 1 unclassifiable lymphoma). All patients achieved clinical complete remission (CR). Of those who completed treatment more than a year ago, three continue to be in CR at 17, 24 & 25 months and two are lost to follow up.

Phase II study of high-dose ifosfamide as a single agent and in combination with cisplatin in the treatment of advanced and/or recurrent squamous cell carcinoma of head and neck.

152 patients with histologically proven squamous cell carcinoma of the head and neck (advanced and/or recurrent) were treated with a single drug therapy of ifosfamide 1.5 g/m2 by intravenous drip for half an hour in 125 ml of dextrose saline for 5 days and mesna 20% of the total ifosfamide dose in 3 doses for 5 days, or in combination with cisplatin 10 mg/m2 by intravenous infusion for 5 days following the ifosfamide drip. The courses of treatment were repeated at the interval of every 4 weeks, and a total of 3 cycles was given. Out of 152 patients 64 received ifosfamide alone, and 88 received ifosfamide with cisplatin. 6 complete and 25 partial remissions (total response 53%) were observed in 58 evaluable patients of the ifosfamide group, and 10 complete and 40 partial remissions (total response 65.7%) were observed in 76 evaluable patients of the combination group. Nausea, vomiting, alopecia and leucopenia were experienced by all patients.

Adjuvant chemotherapy for osteogenic sarcoma of the extremity with sequential adriamycin and cisplatin.

Twenty-nine patients with high-grade nonmetastatic osteogenic sarcoma of the extremities were treated with adjuvant chemotherapy following definitive surgery. Chemotherapy consisted of systemic intravenous Adriamycin and cisplatin in a sequential fashion given for six courses. Nineteen out of 29 patients are alive and continuously disease free over a follow-up period ranging from 9+ to 30+ months. The relapse-free survival was 72%, and overall survival for the entire group was 69%. Median survival is not reached yet. Six out of 29 patients relapsed, of which 1 patient is alive for 6+ months after relapse. Three patients died of chemotherapy toxicity. The results were superior to historical controls treated with surgery alone. The need for more aggressive treatment approaches is discussed.

Prognostic significance of myeloperoxidase containing blast cells in acute myelogenous leukaemia.

Fifty three newly diagnosed patients of de novo acute myelogenous leukaemia (AML) received treatment consisting of remission induction with daunorubicin 60 mg/m2 on day one and continuous infusion of cytosine arabinoside 200 mg/m2/day over 24 h from day one to 7. Thereafter patients in complete remission received consolidation chemotherapy with two identical courses. Complete remission (CR) could be achieved in 40 patients (75.5%). Seven patients (13.2%) died with complications during aplasia phase following remission induction therapy while six patients (11.3%) had resistant disease. Twenty seven patients (67.5%) developed relapse while eight patients (15.1%) continue to remain in complete remission ranging from 51 to 68 months (median 62.5). The projected event free survival and disease free survival at 60 months is 15 per cent (SE + 11.9%) and 21 per cent (+6%) respectively. Evaluation of the prognostic significance of pretherapy characteristics showed that infection at presentation and low number of myeloperoxidase (MPO) containing blasts affected the achievement of complete remission adversely on univariate analysis. Similarly age at diagnosis, of more than 45 yr, total leucocyte count of 50,000/cumm or more and low number of MPO containing blasts affected the remission duration (disease free survival) adversely on univariate analysis. On multivariate analysis, MPO positivity of blast cells, remained the only significant independent characteristic. High MPO positivity affected the remission duration favourably (P < 0.01). Patients with high MPO positivity also achieved CR with one induction cycle in 32 out of 40 instances while only 2 out of 5 patients with low MPO positivity, achieved CR with one chemotherapy cycle (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Four-agent induction/consolidation therapy for childhood acute lymphoblastic leukemia: an Indian experience.

During 1984-1986, a total of 128 children with acute lymphoblastic leukemia (ALL) were treated with an induction-consolidation regimen consisting of doxorubicin, vincristine, cytosine-arabinoside, and prednisolone. One hundred two (80%) patients belonged to high-risk group. The complete remission rate for all the patients was 91%. The event-free survival at 5 years was 32.0% +/- 23%. On multivariate analysis the event-free survival and disease-free survival was not altered by age, sex, WBC count, platelet count, LDH level, and surface phenotype. Infection due to prolonged marrow aplasia was a common complication, leading to mortality of 8 patients during induction and 33 patients during first remission. The relapse rate has been 36% (42 patients). The predominance of high-risk ALL in the Indian population underscores the need for intensive therapy. Improved supportive care during induction and remission seems essential to decrease therapy-related mortality, leading to improved survival.

Alpha-interferon in hairy cell leukemia: an initial Indian experience.

In the last decade, 14 patients were diagnosed as having hairy cell leukemia (HCL) at our hospital; five of these were treated with the biological response modifier, recombinant alpha-interferon (IFN), as their initial treatment. Four of these cases showed a complete remission of the disease while one had a good partial response after a few months of therapy. One case is in unmaintained remission while one has relapsed with a just palpable spleen on stopping the drug; two are still on intermittent IFN therapy while one has been lost to follow up. Fever and skin rash were the most common side effects observed but did not warrant reduction of dose or stoppage of treatment. We conclude that IFN is highly effective and well tolerated as initial treatment of HCL in a country like India. Splenectomy will continue to be the first line therapy in the majority of cases but, in certain selected situations, IFN can be an extremely useful alternative.

Cytotoxic therapy. Role of durable venous access.

Aggressive chemotherapy regimens and supportive measures in haemato-oncology patients demand reliable venous access. Experience with this method in India has been limited. During a period of six months, we have used 42 subclavian indwelling catheters and 31 cubital Cavafix long lines. The mean age of patients in the two groups was 32 years and 7 years respectively. Subclavian catheters had a median duration of catheter placement of 46 days (range 4-145) and total 1494 catheter days, while cubital longlines yielded a median duration of insertion of 14 days (range 4-27) and total 508 catheter days. Catheter related complications were infection in 25% of patients, thrombophlebitis in 22%, blockade in 12% and misplacement in 17% in both groups taken together. The patients and families were extremely satisfied with the devices. Our experience supports further use of durable venous access in cancer patients. Implanted central venous catheters should be preferred whenever feasible.

The spectrum of pancreatic exocrine and endocrine (beta-cell) function in tropical calcific pancreatitis.

Exocrine pancreatic marker (immunoreactive-trypsin) and endocrine Beta-cell function (plasma insulin and C-peptide during an oral glucose tolerance test) were studied in 40 subjects with tropical-calcific-pancreatitis [seven non-diabetic, seven with impaired-glucose-tolerance and 26 diabetic (fibro-calculous-pancreatic-diabetes)]. In non-diabetic and impaired-glucose-tolerance subjects there was evidence of active pancreatitis in some and exocrine function was partially preserved. Fibro-calculous-pancreatic-diabetic subjects showed severely diminished exocrine pancreatic function; none showed 'pancreatitic' elevation of immunoreactive-trypsin. Beta-cell function was preserved in non-diabetic and impaired-glucose-tolerance subjects; diabetic subjects showed variable Beta-cell function but it was severely diminished in more than 75%. Immunoreactive-trypsin and C-peptide were directly correlated (rs = 0.55, p less than 0.01). This cross sectional study demonstrates, for the first time, that the Beta-cell loss in tropical-calcific-pancreatitis is related to the exocrine loss. It suggests that diabetes in tropical-calcific-pancreatitis is either secondary to pancreatitis or that a common factor(s) acts simultaneously on both components.