A phase II study of sequential neoadjuvant gemcitabine plus doxorubicin followed by gemcitabine plus cisplatin in patients with operable breast cancer: prediction of response using molecular profiling.

This study examined the pathological complete response (pCR) rate and safety of sequential gemcitabine-based combinations in breast cancer. We also examined gene expression profiles from tumour biopsies to identify biomarkers predictive of response. Indian women with large or locally advanced breast cancer received 4 cycles of gemcitabine 1200 mg m(-2) plus doxorubicin 60 mg m(-2) (Gem+Dox), then 4 cycles of gemcitabine 1000 mg m(-2) plus cisplatin 70 mg m(-2) (Gem+Cis), and surgery. Three alternate dosing sequences were used during cycle 1 to examine dynamic changes in molecular profiles. Of 65 women treated, 13 (24.5% of 53 patients with surgery) had a pCR and 22 (33.8%) had a complete clinical response. Patients administered Gem d1, 8 and Dox d2 in cycle 1 (20 of 65) reported more toxicities, with G3/4 neutropenic infection/febrile neutropenia (7 of 20) as the most common cycle-1 event. Four drug-related deaths occurred. In 46 of 65 patients, 10-fold cross validated supervised analyses identified gene expression patterns that predicted with >or=73% accuracy (1) clinical complete response after eight cycles, (2) overall clinical complete response, and (3) pCR. This regimen shows strong activity. Patients receiving Gem d1, 8 and Dox d2 experienced unacceptable toxicity, whereas patients on other sequences had manageable safety profiles. Gene expression patterns may predict benefit from gemcitabine-containing neoadjuvant therapy.

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.

Synchronous occurrence of carcinoma of the uterine cervix and of the breast.

The synchronous occurrence of carcinoma of the uterine cervix and the breast is a rarity. We report a case of a 35-year-old woman who had non-keratinizing squamous cell carcinoma of the uterine cervix (FIGO Stage IIb) simultaneously with infiltrating lobular carcinoma of breast (T4bN2M1).

Radiotherapy for desmoplastic fibroma of bone: a case report.

Desmoplastic fibroma is a rare benign tumour of bone. Diagnosis is not easy and is often made by excluding other tumours. Histopathological diagnosis of this tumour is also sometimes not easy. The treatment modalities for this tumour are non-uniform and often controversial. In the present case surgical options were left aside because the patient did not consent to surgery, so radiotherapy was used, with success at 3-year follow-up. This case is presented here along with a review of relevant literature.

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.

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.

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.

Biochemical Changes after Short-term Oral Exposure of Jatropha curcas Seeds in Wistar Rats.

Jatropha curcas (Euphorbiaceae) is a multipurpose shrub with varied medicinal uses and is of significant economic importance. In addition to being the source of biodiesel, its seeds are also considered highly nutritious and could be exploited as a rich and economical protein supplement in animal feeds. However, the inherent phytotoxins present in the seed is the hindrance. The toxicity nature of the seeds of the local variety of J. curcas is not known. Therefore, investigations were undertaken to evaluate the short-term oral toxicity of the seeds of locally grown J. curcas. Short-term toxicity was conducted in rats by daily feeding the basal diet (Group I), and the diet in which the crude protein requirement was supplemented at 25% (Group II) and 50% (Group III) levels through Jatropha seed powder. The adverse effects of Jatropha seed protein supplementation (JSPS) were evaluated by observing alterations in biochemical profiles. The biochemical profile of rats fed on diet with JSPS at both the levels revealed significant reduction in plasma glucose and total protein and increase in plasma creatinine, transaminases (Plasma glutamic pyruvic transaminase and Plasma glutamic oxaloacetic transaminase), and alkaline phosphatase.

A multicenter phase II study of gemcitabine, paclitaxel, and cisplatin in chemonaïve advanced ovarian cancer.

OBJECTIVES: The objectives of this multicenter phase II study were to evaluate the effects of gemcitabine-paclitaxel-cisplatin combination chemotherapy on response rate, survival, and toxicity in patients with advanced epithelial ovarian cancer (AEOC). METHODS: Chemonaive AEOC patients with bidimensionally measurable disease or an elevated serum cancer antigen 125 level received cisplatin (70 mg/m(2)) on day 1 and paclitaxel (80 mg/m(2)) and gemcitabine (1000 mg/m(2)) on days 1 and 8, every 3 weeks. RESULTS: Between October 2000 and September 2001, 46 patients were enrolled. Sixteen patients underwent debulking surgery prior to chemotherapy. In 45 evaluable patients, overall response rate was 64.4% (7 CR and 22 PR). Median time-to-progression was 13.4 months (95% CI, 9.6-17.4 months); median progression-free survival was 12.3 months (95% CI, 8.8-15.6 months); median overall survival was 26.0 months (95% CI, 18 months-not reached); and 1-year survival was 74% (95% CI, 60-88%). The relative dose intensities of gemcitabine, paclitaxel, and cisplatin were 81.4%, 80.2%, and 89.8%, respectively. Grade 3/4 neutropenia was the predominant hematologic toxicity observed (73.9% of patients) followed by grade 3/4 leukopenia (56.5%), anemia (45.7%), thrombocytopenia (23.9%), and febrile neutropenia/neutropenic sepsis (26.1%). The predominant grade 3 nonhematologic toxicities were alopecia (43.5%) and diarrhea (19.6%). Grade 4 nonhematologic toxicities were nausea/vomiting, constipation, and uremia (2.2% each). Two treatment-related deaths occurred (neutropenic sepsis and uremia). CONCLUSION: Gemcitabine-paclitaxel-cisplatin combination chemotherapy is active with manageable toxicity in chemonaive patients with advanced ovarian cancer and should be explored in larger phase III trials.

Carcinoma of the major salivary glands. analysis of the role of radiation therapy.

Forty-six patients of major salivary gland tumors were retrospectively studied. There were 40 (87%) parotid and 6 (13%) sub-mandibular tumors. Patients receiving adjuvant radiation therapy after a radical surgery fared much better (86%) complete response (CR) as compared to those treated for recurrent or inoperable disease (50% CR). The 5-year overall and disease free survival rates for the entire group is 70% and 34% respectively. These findings and a review of literature suggests that adjuvant post operative radition therapy is recommended to reduce the risk of post surgical recurrence.

A study of concurrent radiochemotherapy with paclitaxel in glioblastoma multiforme.

Despite advances in neurosurgery and radiotherapy, the prognosis of patients with glioblastoma multiforme remains poor. Reports in the literature about the radiosensitizing properties of paclitaxel stimulated the authors to conduct a study using paclitaxel concurrently with radiation in a group of 18 patients who had residual disease postoperatively. Paclitaxel was delivered weekly as an intravenous infusion in a dose of 60 mg/m2 along with radiation to the primary lesion. A total of 108 cycles of paclitaxel was given. All the patients tolerated the treatment well. The main side effects were haematological, and neuropathy which was self-limiting. The overall 1-year survival rate was 70%, with 12 patients alive at 13 months. The median survival has not yet been reached although it is more than 13 months. Thus, paclitaxel can be safely delivered concomitantly with radiation in patients with glioblastoma multiforme. Larger, randomized trials are required to establish the comparative efficacy of paclitaxel as a radiosensitizer in glioblastoma multiforme.

A phase II study of gemcitabine and cisplatin in chemotherapy-naive, unresectable gall bladder cancer.

The primary objective of this study was to determine the response rates of the gemcitabine and cisplatin combination in unresectable gall bladder cancer patients. The secondary objectives were to evaluate the toxicity, time to progressive disease, and overall survival. Chemonaïve patients with histologically proven, unresectable bidimensionally measurable gall bladder cancer were enrolled into this study. All patients were required to have a Zubrod's performance status