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Biomedical subjects

D Raghavan

Publications and source records attributed to D Raghavan.

At least 55 records · Page 3Linked to original sources
PubMed1995

Phase I study of paclitaxel and carboplatin: implications for trials in head and neck cancer.

An ongoing phase I and pharmacokinetic trial of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with carboplatin is evaluating the maximum tolerated dose (MTD) of a 3-hour paclitaxel infusion combined with fixed doses of carboplatin in previously treated and untreated patients with a variety of advanced cancers. A patient's previous treatment status determines the fixed carboplatin dose: target area under the concentration-time curves of 4.0 and 4.5 mg.min/mL in previously treated and untreated patients, respectively. Studies 1 and 2 entered previously treated patients to establish the paclitaxel MTD without and with cytokine support: study 1 established 135 mg/m2 paclitaxel as the MTD without such support. In study 2, granulocyte colony-stimulating factor is administered, and the MTD has not yet been reached with paclitaxel doses of 135 mg/m2 to 230 mg/m2 assessed thus far and 250 mg/m2 now being evaluated. Objective responses have been seen in three of five patients with squamous cell carcinoma of the head and neck and in patients with non-small cell lung cancer and metastatic cancer of unknown primary site as well. Myelosuppression has been the dose-limiting toxicity, although significant nausea and vomiting and myalgia have been documented occasionally. Paclitaxel apparently has nonlinear pharmacokinetics with a beta half-life of 6.7 hours (SD +/- 1.3 hours). Future trials of paclitaxel/carboplatin will address the management of squamous cell carcinoma of the head and neck and non-small cell carcinoma of the lung.

Adenocarcinoma↗
PubMed1994

Phase I and pharmacokinetic evaluation of floxuridine/leucovorin given on the Roswell Park weekly regimen.

A phase I and pharmacokinetics study was carried out of floxuridine (FdUrd) modulated by leucovorin (LV) given on the Roswell Park regimen (LV given at 500 mg/m2 by 2-h infusion and FdUrd given by i.v. push at 1 h after the start of LV infusion, treatment being given weekly x 6). The dose-limiting toxicity was diarrhea; the MTD and recommended dose for phase II studies was 1,650 mg/m2 per week of FdUrd. The dose-response curve was steep, with 3/3 patients treated at a dose of 1,750 mg/m2 developing grade IV diarrhea. With this schedule there was no significant mucositis. Pharmacokinetic parameters showed very wide interpatient variability. Plasma decay was biphasic with a t1/2 beta of approximately 2 h. Plasma clearance was high (> 200 1 h-1). No correlation between pharmacokinetic parameters and toxicity could be identified.

Adult↗
PubMed1994

Operation and intracavitary photodynamic therapy for malignant pleural mesothelioma: a phase II study.

From April 1991 to May 1993, 23 patients entered a phase II clinical study of surgical resection and adjuvant intracavitary photodynamic therapy for malignant pleural mesothelioma. Two days preoperatively, patients received an intravenous injection of 2 mg/kg of the photosensitizer Photofrin. Six patients underwent a pleuro-pneumonectomy, and 15 patients a pleurectomy, after which intracavitary photodynamic therapy was administered. A total light energy dose of 20 to 25 J/cm2 was given. In 2 patients the tumor was unresectable due to intrapericardial invasion. Postoperative complications were noted in more than 50 percent of patients; 2 patients died of postoperative complications. Postoperative survival was analyzed according to intraoperative staging proposed by the American Joint Committee for Cancer Staging, published in 1992. The overall estimated median survival is 12 months; that of stage III and IV patients is 7 months. Five patients with stage I and II diseases (who had grossly complete resection by pleurectomy) are alive, disease-free, for 11, 17, 18, 21, and 33 postoperative months. Intraoperative staging is important in carrying out further clinical studies of malignant pleural mesothelioma.

Adult↗
PubMed1994

Karyotypic analysis of a heterogeneous human transitional cell carcinoma of the bladder.

The UCRU-BL-17 (BL-17) series of xenografts, tissue culture sublines, and cloned cell lines (Fig. 1) shows a range of heterogeneous growth characteristics both in vitro and in vivo (Table 1) and represents a model of human bladder cancer heterogeneity. Cytogenetic analysis was undertaken to determine if specific chromosome changes correlated with particular aspects of the heterogeneous phenotypes. The BL-17 sublines and cloned cell lines shared many common chromosome abnormalities. Indeed, the cloned cell lines showed nearly identical karyotypes despite their marked differences in growth characteristics. Karyotypic evolution with passage through the nude mice was apparent, however. This evolution occurred at the specific chromosome regions of 1p12, 3cen-3p21, and 6cen-6q21. Whether the heterogeneity of karyotype between the BL-17 cell lines resulted from the existence of multiple clones in the original patient tumor or from karyotypic instability through passage in nude mice is uncertain, but in either case the specificity of karyotypic evolution observed suggests that 1p12, 3cen-3p21, and 6cen-6q21 are hotspots for rearrangement in the BL-17 tumor. No specific correlations between chromosome abnormalities and biologic characteristics could be made, but several unique karyotypic features arose in the progression to two of the sublines, BL-17/23 alpha and BL-17/0/X2A, coinciding with a loss of anchorage-independent growth by BL-17/23 alpha and a change in growth in vivo from a solid tumor to a fluid-filled tumor by BL-17/0/X2A.

Aged↗
PubMed1994

Multiple atypical nevi: a cutaneous marker of germ cell tumors.

PURPOSE: This study assessed whether a specific association exists between atypical nevi and germ cell tumors (GCT). METHODS: A prospective comparison was performed on a cohort of 129 unselected patients with GCT and a series of 153 healthy men. Three or more of the following criteria were required for diagnosis of multiple atypical nevi: greater than 5 mm in diameter; variegated color, often speckled black/brown, with irregularly distributed pigmentation; irregular outline or indistinct border; and at least three such lesions. RESULTS: Prevalences for multiple atypical nevi in patients with GCT and in healthy controls were 37% and 15%, respectively (P < .01). Two patients with these lesions also had documented malignant melanoma. In contrast, 16% of patients with GCT had a history of testicular maldescent (the most common known risk factor), compared with 5% of healthy controls (P < .01). CONCLUSION: Multiple atypical nevi occur with a statistically significant increased prevalence in patients with GCT as compared with healthy controls, and constitute one of the most common known clinical associations with this malignancy. These data may be of relevance for our understanding of the biology of GCT and of malignant melanoma, in the design of screening programs for testis cancer, and in the follow-up evaluation of patients with each of these disorders.

Adolescent↗
PubMed1994

Carboplatin for small cell lung cancer: progress toward greater efficacy and reduced toxicity.

Small cell lung cancer, an aggressive malignancy characterized by early dissemination, is highly responsive to radiotherapy and cytotoxic chemotherapy. Since the introduction of combined-modality regimens that incorporate both radiotherapy and chemotherapy, the median survival time for patients with localized disease has increased to 12 to 15 months, but median length of survival of patients with extensive disease has remained at a plateau of only 6 to 8 months. New cytotoxic agents, such as ifosfamide, etoposide, and carboplatin, have contributed to a reduced toxicity profile and an increase in complete response rates to combination regimens of 40% to 50%, but they have not contributed to any major increase in long-term survival. Potential strategies for improving efficacy and reducing toxicity of the chemotherapy of small cell lung cancer are reviewed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

A randomised cross-over trial of antiemetic therapy for platinum-based chemotherapy. Improved control with an intensive multiagent regimen.

In a partially blinded randomised cross-over trial, 78 patients receiving cisplatinum based chemotherapy were assigned to receive two forms of antiemetic therapy: SAD, a regimen composed of serenace (haloperidol), ativan (lorazepam), and dexamethasone followed by low dose maxolon (metoclopramide) and STADMAX, a regimen composed of scopolamine (hyoscine), tavegyl (clemastine), ativan, dexamethasone and high dose maxolon. Each antiemetic regimen was given in random order, with the first and second cycles of cytotoxic chemotherapy. 66 (85%) patients completed both cycles of antiemetic therapy and were available for the cross-over comparison. Significantly less acute vomiting, as assessed by nurse observer (P < 0.0001), and less delayed vomiting, as assessed by patient diary (P = 0.03), were seen with STADMAX. In the first 18 h, complete control of vomiting (no episodes) was achieved in 30 (45%) patients with STADMAX compared with 10 (15%) receiving SAD. Overall, major control of emesis (< or = 2 episodes) was achieved in 56 (85%) patients with STADMAX compared with 35 (53%) receiving SAD. Vomiting was also better controlled on STADMAX in the week after this initial 18 hour period based on the 7 day patient diary with no vomiting episodes in 18/65 (28%) on STADMAX vs. 13/65 (20%) on SAD. However, no significant differences in appetite, nausea or vomiting were found when based on linear analogue self assessment (LASA) scales recorded by patients. Significant differences in side effects of the two antiemetic regimens were noted on LASA scales with more dry mouth (P = 0.01), blurred vision (P = 0.03) and diarrhoea (P = 0.04) associated with STADMAX and more restlessness (P = 0.002) associated with SAD. Significantly, no episodes of dystonic reactions were seen among patients on either regimen. In the 68 patients who completed both cycles and were in a position to express a preference, 46 (68%) preferred STADMAX compared with only 20 (29%) who preferred SAD (P = 0.001), while 2 patients expressed no preference. It is concluded that STADMAX is the preferred regimen to SAD for the control of cisplatinum-related emesis. It has a role, both where specific serotonin 3 antagonists are not available and as a model for building more effective combinations where these agents are available.

Adult↗
PubMed1993

Characterization of a new human bladder cancer cell line, UCRU-BL-28.

A new human bladder cancer cell line, UCRU-BL-28 has been established and characterized from a relapsed, cisplatin resistant, grade II, stage T4 tumor. This line is tumorigenic in nude mice and reflects the pathology of the original tumor. The morphology, the expression of tumor-associated antigens and EGF receptors, and the ability to grow both in an anchorage independent manner and in the absence of serum is explored. The BL-28 line has 71-74XXY chromosomes, with del 5q, der(9) and i(19q). Further studies on the molecular basis of bladder cancer, chemosensitivity to cisplatin, growth factor production and tissue invasion are under way.

Biomarkers, Tumor↗
PubMed1993

The impact of histological review on clinical management of testicular cancer.

Accurate histological diagnosis and staging are critically important in determining the optimal management of patients with testicular cancer. We have assessed the importance of histological review of "outside" pathology reports from 87 patients referred to the Urological Cancer Research Unit. In 28 patients (32%), the reviewed pathology report differed from the outside report. In 10 of these patients (11%), the pathology review resulted in a change of treatment or prognosis from that which would have obtained in the absence of such histological review. Pathology review at a major cancer centre with a subspecialist interest in tumour pathology and a large experience in the management of germ cell malignancy is an essential first step in the treatment of testicular cancer.

Adult↗
PubMed1993

Oral cyclophosphamide for the management of hormone-refractory prostate cancer.

Thirty patients with hormone-refractory prostate cancer were treated with cycles of oral cyclophosphamide (100 mg/m2/day for 14 days, with a 14-day gap). Eighteen patients had a significant improvement in symptoms of advanced disease, 6 had objective partial remissions and 13 had stabilisation of disease (criteria of National Prostatic Cancer Project). The median survival from the time of diagnosis was 33.3 months, and from the commencement of cyclophosphamide 12.7 months. The treatment was well tolerated. oral cyclophosphamide is active in the treatment of advanced hormone-refractory prostate cancer and yields symptomatic and objective remissions without undue side effects. This observation requires validation, with further testing of its impact on survival in randomised clinical trials.

Administration, Oral↗
PubMed1993

The importance of bleomycin in combination chemotherapy for good-prognosis germ cell carcinoma. Australasian Germ Cell Trial Group.

PURPOSE: In an effort to maintain the excellent long-term results achieved with combination chemotherapy for good-prognosis germ cell carcinoma, but to reduce the toxicities encountered, a randomized trial was conducted comparing cisplatin and vinblastine with or without bleomycin. PATIENTS AND METHODS: Two hundred eighteen assessable patients with a good prognosis were randomized to receive induction chemotherapy with cisplatin 100 mg/m2 intravenously (IV) day 1 and vinblastine 6 mg/m2 IV days 1 and 2 every 3 weeks (PV) with or without bleomycin 30 mg intramuscularly (IM) weekly (PVB) for a maximum of 12 weeks. Once maximum response was achieved, patients with a complete remission (CR) received two courses of consolidation chemotherapy, while those with residual abnormalities and normal tumor markers underwent surgical resection whenever possible. RESULTS: Toxicities encountered in this study were clearly greater for those patients who received bleomycin, with significantly more leukopenia, thrombocytopenia, anemia, alopecia, and renal and pulmonary toxicities. The proportion of patients who achieved CR and had no evidence of disease (resection of all viable malignancy) was 89% for PV and 94% for PVB (P = .29). After a minimum of 4 years of follow-up, relapses have occurred in 7% of patients who received PV and 5% who received PVB. A total of five patients on each therapy arm were successfully treated with further salvage chemotherapy and surgery. Thus, deaths from progressive malignancy have occurred in 15% of patients on PV and 5% on PVB (P = .02), a rate that was partly offset by the higher proportion of toxic deaths with PVB (P = .06). CONCLUSION: Despite the toxicities encountered with bleomycin in cisplatin-based combination chemotherapy for these patients, complete deletion of this drug compromises therapeutic efficacy.

Adolescent↗