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.

Effect of amifostine on toxicities associated with salvage combination chemotherapy.

PURPOSE: To determine the effect of amifostine on the safety and efficacy of chemotherapy in heavily pretreated patients and to study the side effects of amifostine delivered to patients receiving chemotherapy at a dose of 740 mg/m2. MATERIAL AND METHODS: Thirty-two patients of histologically proven (recurrent) malignancy who had previously received > or = 6 cycles of chemotherapy and developed grade II or grade III toxicities during treatment with salvage chemotherapy were eligible. These patients were given Injection Amifostine 740 mg/m2 as a 15 min. i.v. infusion 30 min. prior to combination chemotherapy. RESULTS: A total of 85 cycles were administered with amifostine and 46 cycles without amifostine. The side effects during amifostine infusion were hypotension (9.6% cycles), vomiting (20% cycles), somnolence (33% cycles), sneezing (8% cycles), and flushing (19% cycles). The chemotherapy toxicities were reduced from 47.7% to 30.6% for grade II and from 28% to 9.4% for grade III in case of gastrointestinal toxicity. Similarly there was improvement in the mean hemoglobin level from 8.2 gm% to 10.01 gm%, mean total leucocyte count from 2,280/mm3 to 3,600/mm3. CONCLUSION: Amifostine has an excellent safety profile and is well tolerated by the patients. Pretreatment with Amifostine resulted in fewer treatment related delays and dose reduction resulting in better tolerance to salvage chemotherapy.

Paclitaxel-epirubicin in advanced breast cancer.

Breast cancer remains a major cause of morbidity and early death in women worldwide. Despite the responsiveness of advanced breast cancer to a number of chemotherapeutic and hormonal agents, long term outcome remains poor. The introduction of paclitaxel with a novel mechanism of action has kindled a ray of hope. Combination of paclitaxel with anthracyclines are being tried, with varying degree of success. Twenty patients with metastatic or locally advanced breast cancer were treated with Paclitaxel (175 mg/m2) and Epirubicin (80 mg/m2) administered sequentially. Each patient received 3 to 6 such cycles at 3 weekly intervals. A response rate of 85% (95% Confidence Interval (CI) 69%-100%) was observed in these patients with 25% (95% CI 6%-44%) achieving complete response. A response rate of 100% was observed in the six patients with locally advanced disease who had not received any chemotherapy earlier. Grade III neutropenia occurred in 5 patients and was reversible in all the cases. This combination is well tolerated. Its efficacy is being compared in a randomised trial with CAF regime in advanced breast cancer in our center.

Simultaneous radiochemotherapy in the treatment of inoperable, locally advanced head and neck cancers.

The results of radiation therapy alone in locally advanced head and neck cancers are dismal with 5 year locoregional control rates not exceeding 15%. The addition of concomitant chemotherapy with cisplatin and more recently carboplatin has shown promising results. Twenty patients of inoperable stage III and IV oral or oropharyngeal cancers were treated with concomitant chemoradiation with carboplatin 300 mg/m2 i.v. on days 1, 21 and 42 of radiation therapy. Twelve (60%) patients had a complete remission. Thirteen patients were alive at a median follow up of 11 months. The treatment was well tolerated with only 2 patients requiring treatment interruptions for mucositis. Longer follow up would reveal any improvement in overall survival. The relative ease with which carboplatin/RT was administered suggests that other agents might be added as well.

Medulloblastoma--a retrospective analysis.

A retrospective review of 45 patients was undertaken at the All India Institute of Medical Sciences to assess the outcome and prognostic factors for these patients who received post operative radiotherapy with or without chemotherapy for medulloblastoma. The median age at diagnosis was 11 years, with 34 males and 11 female patients. Thirty four tumours were confined to midline structures, and 11 were localised to one cerebellar hemisphere or involved midline and lateral structures. Complete macroscopic removal was achieved in 24 patients and subtotal removal in 21 patients. Forty one patients underwent craniospinal irradiation and 27 patients received adjuvant chemotherapy. Median overall and disease free survival was 57 and 31 months respectively and 3 year overall survival was 76%. The addition of adjuvant chemotherapy was a significant factor for disease free survival (p = 0.01) whereas extent of surgery (total vs subtotal, p = 0.01) was a significant factor for overall survival only. Eleven patients developed recurrent disease, with ten relapsing first in the posterior fossa.