Biomedical subjects

C Plager

Publications and source records attributed to C Plager.

At least 55 records · Page 3Linked to original sources

PubMed1997

High-dose ifosfamide in bone and soft tissue sarcomas: results of phase II and pilot studies--dose-response and schedule dependence.

PURPOSE: To evaluate the efficacy and feasibility of high-dose ifosfamide (HDI) at a total dose of 14 g/m2 per cycle with mesna in combination with granulocyte colony-stimulating factor (G-CSF) in adult patients with sarcomas. PATIENTS AND METHODS: Between July 1991 and February 1994, 74 patients with sarcomas (37 bone and 37 soft tissue) were treated on two simultaneous phase II studies that evaluated HDI given as a continuous infusion over 74 hours. G-CSF was started on day 5 at 5 microg/kg/d until recovery of granulocyte count. Additionally, between March 1993 and March 1994, 15 similar patients with previously treated bone or soft tissue sarcomas were treated on a pilot study in which the same total dose of ifosfamide was administered by a bolus schedule, along with mesna and G-CSF. Patients were treated until maximal response, and where possible, surgical resection of gross disease was performed. RESULTS: Seventy-two patients from the phase II study using continuous infusion are assessable for response. Four complete responses (CRs) and 17 partial responses (PRs) were noted, for an overall response rate of 29% (95% confidence interval [CI], 19% to 39%). The response rate was 40% (95% CI, 24% to 56%) for bone sarcomas and 19% (95% CI, 6% to 32%) for soft tissue sarcomas. Fourteen patients from the pilot study that used a bolus schedule are assessable for response. One CR and seven PRs were noted, for an overall response rate of 57% (95% CI, 31% to 83%) and a response rate of 45% for soft tissue sarcomas. Two patients developed grade 3 to 4 renal toxicity, three developed grade 3 CNS toxicity, one had possible grade 3 cardiac toxicity, and two developed severe painful peripheral neuropathy. There were no treatment-related deaths. CONCLUSION: HDI at 14 g/m2 with mesna and G-CSF is an active salvage regimen for patients with bone and soft tissue sarcomas. There is a definite positive dose-response curve, and bolus administration appears to be more active than continuous infusion.

Adolescent↗

PubMed1997

Development and results of biochemotherapy in metastatic melanoma: the University of Texas M.D. Anderson Cancer Center experience.

PURPOSE: Systemic therapy for metastatic melanoma includes chemotherapy, either with dacarbazine alone or a multiagent combination regimen, and biologic therapy with recombinant interferon-alpha and/or recombinant interleukin-2. However, neither of these treatment options has produced long-term control of disease except on rare occasions. We have therefore developed a combined biochemotherapy program in an effort to improve long-term control of metastatic melanoma. PATIENTS AND METHODS: Between October 1990 and October 1993, we treated 115 patients with a triple-drug chemotherapy regimen--CVD (cisplatin, vinblastine, dacarbazine)--in combination with biotherapy using recombinant interleukin-2 and recombinant interferon-alpha. This program of biochemotherapy has evolved from an initial protocol of sequential use of CVD followed by biotherapy, called sequential biochemotherapy, to a more recent protocol of concurrent administration of all five drugs, called concurrent biochemotherapy. Sixty-two patients have been treated with the sequential regimen and 53 patients with the concurrent regimen. RESULTS: Among the 114 evaluable patients, we have observed 24 complete responses (21%) and 45 partial responses (39%) for an overall response rate of 60%. From the group of 24 complete responders, 12 patients (10% of the total) have achieved long-term remissions and have remained disease free for periods of time ranging from 4+ to 6+ years. CONCLUSION: Although the overall results of sequential versus concurrent biochemotherapy are similar, the toxicity appears to be less severe in patients treated with the concurrent regimen. The overall median survival of patients treated with biochemotherapy appears to be longer compared with our previous experience with CVD chemotherapy used alone (12 vs 9 months). Based on the encouraging results obtained with biochemotherapy, phase III studies have been initiated to compare prospectively biochemotherapy with chemotherapy (CVD regimen) alone.

Adolescent↗

PubMed1996

Phase II study of paclitaxel in patients with previously treated osteosarcoma and its variants.

BACKGROUND: Patients with osteosarcoma and its variants who did not respond to standard chemotherapy including doxorubicin, ifosfamide, cisplatin, and high dose methotrexate were treated with paclitaxel so that its therapeutic activity in these patients could be determined. METHODS: We conducted a Phase II study of paclitaxel in patients with conventional osteosarcoma (10), malignant fibrous histiocytoma of the bone (3) and dedifferentiated chondrosarcoma (2) whose disease had progressed after prior standard chemotherapy including doxorubicin, cisplatin, ifosfamide, and high dose methotrexate. Paclitaxel was administered at a starting dose of 175 mg/m2 as a 24-hour infusion with standard premedication every 21 days or upon hematologic recovery (absolute granulocyte count [AGC] > 1500/microliters, platelets > 100,000/microliters). Neupogen was not used routinely. The study was conducted based on a two-stage design. A total of 17 patients were entered into the protocol. Two were ineligible since they had Ewing's sarcoma. Responses were assessed radiographically and pathologically when feasible, using standard criteria. RESULTS: Fifteen eligible patients were treated in the first stage of the study. Median age of the patients was 31 years (range, 19-61 yrs). There were 8 females and 7 males with a Zubrod performance status of 0 or 1. One patient achieved a mixed response and 14 developed progressive disease. Median AGC nadir was 0.3, on Day 13, lasting 5 days. Median platelet nadir was 134, on Day 8. There were no Grade III or IV nonhematologic toxicities and no deaths related to treatment. CONCLUSIONS: Paclitaxel, at this dose and schedule, is well tolerated but inactive in this patient population.

Adult↗

PubMed1996

Evaluation of interleukin-2 administered by continuous infusion in patients with metastatic melanoma.

BACKGROUND: Interleukin-2 (IL-2) has been used widely in the treatment of advanced melanoma, most often using a high dose bolus schedule of administration. We have evaluated the antitumor activity and toxicity of IL-2 when administered by a continuous infusion schedule in patients with metastatic melanoma. METHODS: Thirty-three patients with metastatic melanoma were treated with IL-2 using the maximum tolerated dose level of 12 x 10(6) IU/m2 as a continuous infusion over 24 hours x 4d/week for 4 weeks every 6 weeks. All patients but one had previously received and failed chemotherapy and had evidence of progressive disease. They were required to have normal organ functions and a performance status of 0 to 1. RESULTS: We observed 1 complete response and 6 partial responses among 31 evaluable patients for a response rate of 22% (95%, confidence interval; 10% to 41%). The median response duration was 6 months, with a range of 4 to 18 months. The toxicity of IL-2 was severe but manageable on the general inpatient ward. One patient died of hepatic necrosis that was probably related to IL-2. Five patients required dose reduction of IL-2 due to toxicity in the form of hepatic or renal insufficiency, which was rapidly reversible. CONCLUSIONS: IL-2, used as a continuous infusion at a dose level of 12 x 10(6) IU/m2/day, 4 times every week for 4 weeks, has activity against metastatic melanoma similar to that reported with high dose IL-2 given in a bolus schedule.

Adult↗

PubMed1996

Treatment of metastatic melanoma with combined chemotherapy containing cisplatin, vinblastine and dacarbazine (CVD) and biotherapy using interleukin-2 and interferon-alpha.

BACKGROUND: Metastatic melanoma is commonly treated with chemotherapy and/or biological agents used separately. In this study we have investigated the efficacy of combined chemotherapy using cisplatin, vinblastine, DTIC (CVD) and biological therapy using interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) in patients with metastatic melanoma. PATIENTS AND METHODS: All patients had advanced, inoperable melanoma without prior treatment with chemotherapy or biotherapy, a performance status of ECOG 0-2 and no evidence of symptomatic brain metastases. The CVD regimen consisted of cisplatin 20 mg/m2/d x 4, vinblastine 1.6 mg/m2/d x 5 and DTIC 800 mg/m2 x 1, repeated at 21-day intervals. The biotherapy regimen included IL-2, 9 x 10(6) IU/ m2/d x 4 days and IFN-alpha 5 x 10(6) U/m2/d SC x 5 days. The CVD and biotherapy regimens were integrated initially, in an alternating manner at 6-week intervals and subsequently, in a sequential fashion where patients were randomized to receive either CVD immediately followed by biotherapy (CVD/Bio) or the reverse sequence (Bio/CVD). Patients were admitted to the hospital for IL-2 administration and for monitoring and treatment of IL-2 induced side effects. The phase II results of the integrated therapy (biochemotherapy) studies were retrospectively compared to our previously reported results with the CVD regimen used alone. RESULTS: The alternating biochemotherapy program was used in 40 patients and the sequential biochemotherapy was used in 62 patients. The alternating regimen produced 2 CRs and 11 PRs for an overall response rate of 33% among 39 evaluable patients. The sequential biochemotherapy produced 14 CRs and 23 PRs for an overall response rate of 60% (95% CI, 47% to 72%). The sequence of CVD/Bio resulted in a higher response rate (11 CRs + 11 PRs (69%)) compared to the Bio/CVD sequence (3 CRs + 12 PRs (50%)). Although the duration of PRs was short (median, 8 months), the median duration of CRs was 3+years and 10 of 16 CRs are currently disease free for periods of 3+ to 6+ years. The median survival of patients receiving sequential biochemotherapy was 13 months compared to 9 months for the CVD treated group (P = 0.04). Treatment with biochemotherapy was associated with severe toxicity including intense myelosuppression, infections, IL-2 induced constitutional toxicity and hypotension. However, the IL-2 induced toxicities were generally manageable on a regular ward, except for 15% of the patients who required transfer to an intensive care unit for treatment of complications associated with the treatment. CONCLUSIONS: The sequential combination of CVD with IL-2 + IFN-alpha appears to have produced an increase in the number of durable responses in patients with metastatic melanoma. The toxicity of this program, although severe, was manageable. The biochemotherapy regimen produced an apparent increase in the median survival compared to that observed with the CVD regimen. However, a prospective comparison of these two regimens will be required to confirm these observations.

Adult↗

PubMed1995

Treatment of uveal melanoma metastatic to the liver: a review of the M. D. Anderson Cancer Center experience and prognostic factors.

BACKGROUND: Liver metastasis develops in approximately two-thirds of patients with recurrent uveal melanoma. Despite therapy, the median survival of those with liver metastasis is 5 to 7 months. The recognition of a grave prognosis associated with liver metastasis has led to evaluation of new modalities of therapy, including the use of regional therapies such as intrahepatic arterial chemotherapy and either embolization or chemoembolization of hepatic metastases. In this study, the results of an institutional experience over the past 2 decades are reviewed and prognostic factors that affect survival from the time the liver metastasis is diagnosed are assessed. METHODS: In this study of 201 patients with uveal melanoma involving the liver who were treated at M. D. Anderson Cancer Center between 1968 and 1991, the authors restrospectively reviewed the cases and compared the results of systemic therapies, hepatic intra-arterial chemotherapies, and chemoembolization of liver metastases. Cox's multivariate analysis and stepwise logistic regression were then computed to determine significant prognostic variables. RESULTS: The systemic therapies produced a response rate of less than 1%. Chemoembolization was the most effective treatment, inducing responses in 36% of patients. Survival curves were calculated using the life-table method of Kaplan and Meier. Patient- and tumor-related characteristics were examined and their relation to on survival from the time of diagnosis of liver metastasis was determined. Levels of serum alkaline phosphatase, total bilirubin, and lactic dehydrogenase plus response to treatment showed a strong relation to survival. In contrast, univariate analysis showed that patient age and gender, metastasis free interval, presence of extrahepatic metastasis, and type of therapy for liver metastasis did not influence survival. Multivariate stepwise regression analysis identified serum alkaline phosphatase and metastasis free interval as the main independent prognostic factors for survival after liver metastasis diagnosis. CONCLUSIONS: Of the three modalities of therapy used for choroidal melanoma metastatic to the liver, only chemoembolization using cisplatin-based regimens produced a meaningful response rate. Information from this analysis can be used to predict the outcome of patients with uveal melanoma metastatic to the liver. Patients with metastatic ocular melanoma confined to the liver should be treated with chemoembolization and should not be included in chemotherapy trials designed for cutaneous melanoma.

Adult↗

PubMed1995

In vivo biologic effects of PIXY321, a synthetic hybrid protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 in cancer patients with normal hematopoiesis: a phase I study.

PIXY321 is a novel fusion protein of recombinant human granulocyte-macrophage colony-stimulating factor and interleukin-3 that exhibits biologic effects of both its parent cytokines in vitro and in preclinical studies. To evaluate the clinical safety and hematopoietic effects of this hybrid cytokine, PIXY321 was administered by subcutaneous injection twice daily at doses of 25 to 1,000 micrograms/m2/day over 14 days to 24 patients with sarcoma before chemotherapy as part of a phase I trial. The treatment was associated with significant increases in white blood cell, neutrophil, platelet, and reticulocyte counts (all P < .001). The increase in neutrophil count was dose-related and was seen during treatment with the cytokine, whereas the increase in platelet count was gradual and peaked after the cessation of the cytokine treatment and was not clearly dose related. PIXY321 treatment also increased bone marrow (BM) cellularity and the percentage of BM cells in S phase (P < .001). In addition, there was a significant increase in the number of CD34+ cells and committed and multipotential progenitors in the peripheral blood. The ex vivo expansion capacity of peripheral blood and BM progenitor cells was preserved after the in vivo treatment with PIXY321. The treatment was well tolerated, with the most common side-effect being injection site reactions. The results of this study show the biologic and clinical activity of a genetically engineered fusion molecule of two hematopoietic cytokines in humans with normal hematopoietic function.

Agranulocytosis↗

PubMed1995

Myxoid malignant fibrous histiocytoma: experience with chemotherapy.

Myxoid malignant fibrous histiocytoma (MFH) is an intermediate grade tumor with a definite metastatic potential but a relatively indolent natural history compared to the pleiomorphic variant of MFH. Little is known about its sensitivity to chemotherapy. We reviewed our experience with chemotherapy in myxoid MFH between 1986 and 1992. The patient population was identified through a search of the database maintained by the Departments of Melanoma-Sarcoma Medical Oncology and Pathology: 55 patients with histologically confirmed diagnosis of myxoid MFH were identified. Chemotherapy was administered to 18 of these patients (10 females, 8 males). The median age was 65 (range: 30-76). Ten patients had an extremity primary, seven had a trunk or retroperitoneal primary, and one patient had head and neck as the site of primary tumor. The median size of the primary tumor was 11 cm (range: 5-23 cm) in maximum dimension. Seven patients received chemotherapy in the neoadjuvant setting, eight received it for recurrent or metastatic disease, and three received it postoperatively after complete resection of the tumor. All patients received doxorubicin and dacarbazine with or without cyclophosphamide. Of the 15 patients evaluable for response, 4 achieved an objective response (one CR, 3 PRs, RR = 27%) to a median of 3 cycles (range: 1-7 cycles). At the time of last follow-up, eight patients are alive with no evidence of disease, two patients are alive with disease, and eight patients have expired. The median follow-up is 51 months (range: 26-216 months) from diagnosis. The relatively small sample precludes any definitive conclusions; however, it seems that doxorubicin- and dacarbazine-based chemotherapy has modest activity in myxoid MFH.

Adult↗

PubMed1994

Pilot study of preoperative chemotherapy with cisplatin, vinblastine, and dacarbazine in patients with local-regional recurrence of melanoma.

BACKGROUND: Because the prognosis of patients with local-regional recurrence of melanoma treated with surgery alone usually is poor, the authors conducted a study designed to determine the efficacy of preoperative chemotherapy using cisplatin, vinblastine, and dacarbazine (CVD) in this patient population. METHODS: Eligibility included biopsy-proven, measurable, and potentially resectable local-regional disease in the form of lymph node metastases, satellite/in-transit metastases and/or local recurrence. CVD consisted of cisplatin, 20 mg/m2 intravenously (IV) on days 2-5; vinblastine, 1.6 mg/m2 IV on days 1-5; and dacarbazine, 800 mg/m2 IV on day 1 only, repeated every 3 weeks. Patients usually received two to three courses of CVD and then underwent surgery. Postoperatively, patients who responded continued CVD for a maximum of 8 courses; nonresponders received no further therapy. RESULTS: Of 52 consecutive patients (40 with lymph node involvement and 12 with skin metastases), 5 (10%) achieved a pathologic complete response and 20 (38%) achieved a partial response, for an overall response rate of 48% (95% confidence interval, 34-62). Of the five patients who achieved a pathologic complete response, three had attained a clinical complete response and one a partial response, and one had stable disease after initial chemotherapy. At a median follow-up of 54 months (range, 32-69 months), 38% of the patients remained disease free. CONCLUSION: Preoperative chemotherapy with CVD has significant activity in local-regional recurrences of melanoma, resulting in pathologic complete response in 10% of the patients. Because its impact on survival remains unclear, this treatment strategy should currently remain investigational. Preoperative chemotherapy, however, could be offered to certain patients with bulky, borderline resectable, regional disease for whom cytoreduction may make surgery easier or less mutilating.

Adult↗

PubMed1994

Myxoid liposarcoma. Experience with chemotherapy.

BACKGROUND: Myxoid liposarcoma (ML) is the most common type of liposarcoma. It has been classified as an intermediate grade tumor with a definite metastatic potential but a relatively indolent natural history. Little is known about its sensitivity to chemotherapy. METHOD: The authors reviewed their experience with chemotherapy in ML from 1986 to 1992. The patient population was identified through a search of the database maintained by the Department of Melanoma-Sarcoma Medical Oncology of the M.D. Anderson Cancer Center. RESULTS: Forty-four patients each with a histologically confirmed diagnosis of ML were identified. Twenty-one were treated with chemotherapy. The median age was 45 years (31-69 years); there were 14 men and 7 women. The ML in 19 patients was in the lower extremity, one in the head and neck, and one pelvic. The median size of the primary tumor was 15 cm (range, 7-48 cm) in maximum dimension. Of the 18 patients who received doxorubicin- and dacarbazine-based chemotherapy as a frontline regimen [median of 3 (2-9) cycles] and were evaluable for response, 8 (1 completed response, 7 partial responses) achieved an objective response (44%, 95% confidence interval 21-67%). Two of the remaining three patients who were also treated with a similar regimen were not evaluable for response (one received chemotherapy postoperatively, and the other received concomitant radiation and doxorubicin), and the third patient received ifosfamide as frontline chemotherapy because of a significant cardiac history. Seven patients received chemotherapy in the neoadjuvant setting, 13 for recurrent or metastatic disease, and 1 postoperatively after complete tumor resection. At the last follow-up, 10 patients were alive with no evidence of disease, 3 were alive with disease, and 8 had died. The median follow-up was 51 months (range, 6-199 months) from diagnosis. CONCLUSION: The authors conclude that doxorubicin- and dacarbazine-based chemotherapy is effective in the treatment of ML.

Adult↗

PubMed1994

A phase I trial of weekly lomustine in patients with advanced cancer.

BACKGROUND: Lomustine is a commercially available chloroethyl nitrosourea compound whose antitumor activity in vitro and in animal tumor models exceeds its activity in humans. Part of the poor clinical performance of this drug may be explained by dose-limiting subjective toxicity observed with the standard schedule of one oral dose of approximately 130 mg/m2 every 6-8 weeks. METHODS: Twenty patients were enrolled in a Phase I clinical trial of weekly oral lomustine. The first dose level was 24 mg/m2, with subsequent dose increases in increments of 6 mg/m2. Intrapatient dose escalations were allowed if there were no toxic reactions noted after 12 weekly doses. RESULTS: The dose-limiting toxic effect was the development of thrombocytopenia in 35% of patients (6 of 17) treated at 30 mg/m2 after a median of 12 weekly doses (range, 5-20 weeks), whereas in 18% of patients (3 of 17), neutropenia developed after a median of 12 weeks (range, 9-22 weeks). Grade 3 or Grade 4 hematologic toxicity developed in three of three patients whose doses were escalated to 36 mg/m2/week after showing no evidence of toxicity for 12-16 weeks at 30 mg/m2/week. Partial remission was observed in two patients with malignant melanoma, and stable disease was observed in two patients with hypernephroma. Nausea, vomiting, and malaise were not significant complications of treatment. CONCLUSION: Lomustine can be administered at a dose of 30 mg/m2/week for 12+ weeks to patients with cancer who have received previous treatment with minimal toxicity while retaining antitumor activity.

Administration, Oral↗

PubMed1994

Mechanism of the anti-tumour effect of biochemotherapy in melanoma: preliminary results.

During the conduct of a biochemotherapy trial in which cisplatin, vinblastine and dacarbazine (CVD) were administered concurrently with interleukin-2 (IL-2) plus interferon-alpha 2a (IFN-alpha 2a) (biochemotherapy) in advanced melanoma, we performed a series of laboratory studies in an attempt to understand better the mechanism of anti-tumour effect of the regimen. We initially hypothesized that CVD enhanced the anti-tumour effect of the biotherapy. However, in the first 10 patients studied, of whom eight were responders, we observed no lymphokine-associated killer cell (LAK) and minimal natural killer (NK) cell activities. This prompted us to change our initial hypothesis. Based on the work of others which showed a marked synergism between IL-1 alpha and cisplatin, apparently mediated by H2O2 derived from tumour-infiltrating macrophages, we reasoned that the biotherapy could enhance the cytotoxicity of the CVD regimen. To evaluate macrophage function, we measured serum neopterin levels in eight responders and seven non-responders. An increase of six or more times above baseline levels was observed in seven out of eight responders but in only two of seven non-responders (P = 0.041). We also examined the level of DNA inter-strand cross-link in peripheral blood mononuclear cells in four responders and four responders, as a means to evaluate the DNA repair process. A DNA cross-link index > or = 0.75 was observed in all four responders but only in one non-responder (P = 0.14). Our preliminary results suggest that concurrent biochemotherapy may exert its predominant anti-tumour effect by direct cytotoxicity and that macrophages may be involved in this process.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Effects of PIXY321, a granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein, on chemotherapy-induced multilineage myelosuppression in patients with sarcoma.

PURPOSE: To evaluate the clinical safety and ability of PIXY321, a novel fusion protein of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), to ameliorate chemotherapy-induced multilineage myelosuppression. PATIENTS AND METHODS: PIXY321 was administered by subcutaneous injection twice daily (25 to 1,000 micrograms/m2/d) over 14 days to 24 chemotherapy-naive patients with sarcoma in a phase I/II study. Three weeks from the initiation of PIXY321, the first cycle of chemotherapy with cyclophosphamide, doxorubicin, and dacarbazine (DTIC) (CyADIC) was administered over 3 days. Four weeks later, a second cycle of CyADIC was administered, followed by 14 days of PIXY321. RESULTS: Treatment with PIXY321 was well tolerated. Local skin reactions and constitutional symptoms were the main side effects. The dose-limiting toxicity was not encountered; however, headache and fatigue were more frequent at the highest dose (1,000 micrograms/m2). PIXY321 before chemotherapy elicited a modest increase in the WBC count (consisting mainly of mature neutrophils), platelets, and corrected reticulocyte counts (all P < .001). Following chemotherapy, PIXY321 at effective doses (500 to 1,000 micrograms/m2/d), significantly reduced both the degree (mean nadir, 70 v 310/microL; P = .016) and duration (mean days < 500/microL, 6.6 v 3.9 days; P = .002) of neutropenia. Cumulative thrombocytopenia was not observed during the first two cycles of CyADIC (mean nadir platelet count, 103 v 95 x 10(3)/microL, in cycles no. 1 and 2, respectively; P = NS). Compared with our historic control data, the mean nadir platelet count in cycle no. 2 was significantly higher after PIXY321 (1.7-fold, P < .05) than with CyADIC alone or with GM-CSF support. There was a suggestion for a dose response, since the mean percentage change in nadir platelet values from cycle no. 1 to cycle no. 2 increased with the PIXY321 dose (P < .02), with the peak effect observed at 750 micrograms/m2/d. CONCLUSION: These results suggest a potential clinical role for PIXY321 in attenuating the cumulative multilineage hematopoietic toxicity of chemotherapy.

Adult↗

PubMed1993

Phase II study of vindesine and dacarbazine with or without non-specific stimulation of the immune system in patients with metastatic melanoma.

A single dose of dacarbazine (DTIC), followed by a 5-day intravenous infusion of vindesine (VDS) was administered every 3 weeks to 103 patients with metastatic melanoma. One half of the patients were randomised to receive intravenous methanol extraction residue (MER) of bacillus Calmette-Guerin (BCG) in addition to chemotherapy, on days 7 and 14 of each course. 98 patients were evaluable. The response rates in treatment groups were 16 and 17%, respectively (confidence interval 9-24%). Neither the response rate nor the survival improved when MER was added to chemotherapy. Toxicity was moderate except for a significant granulocytopenia. The combination of DTIC and VDS is not more effective than DTIC alone and has added neurotoxicity.

Adolescent↗

PubMed1990

Beta-lactam regimens for the febrile neutropenic patient.

A total of 535 evaluable febrile episodes in neutropenic patients were randomly assigned to treatment with ticarcillin-clavulanate plus vancomycin (TV), ceftazidime plus vancomycin (CV), or all three antibiotics (TCV). The TCV regimen was significantly more effective than TV, considering all evaluable episodes, documented infections, gram-negative infections, and infections in patients with persistent severe neutropenia (less than 100 neutrophils/mm3). The results with CV were intermediate between TV and TCV. The toxicities were similar with all three regimens and consisted primarily of skin rashes. The TCV regimen is effective for empiric therapy of fever in neutropenic patients and probably should be utilized in preference to CV or TV, although its superiority over CV in this study was inconclusive.

Adolescent↗

PubMed1990

Intracarotid cisplatin-based chemotherapy in patients with malignant melanoma and central nervous system (CNS) metastases.

Twenty-three patients with malignant melanoma metastatic to the central nervous system (CNS) were treated with intracarotid cisplatin-based chemotherapy. Twenty-two had failed prior cranial radiation therapy (one patient refused radiation therapy) and had progressive brain metastases documented by computerized tomography (CT). Intracarotid cisplatin 40-75 mg/m2 was administered alone (seven patients) with 1,3-bis(2-Chloroethyl)-1-nitrosourea (BCNU) (13 patients) or bleomycin (three patients). Courses were repeated monthly with CT scan. Seven patients (30%) had objective improvement in CT scans and three patients (13%) had stabilization of disease. The median time to tumor progression for responding patients was 20 weeks (range 8-34 weeks) while stable disease ranged from 9-12 weeks. In three patients the extracranial disease progressed while the brain metastases responded. Neurological and retinal toxicity were potential complications of therapy. Intracarotid cisplatin-based chemotherapy may be useful for palliation in selected patients with malignant melanoma and CNS metastases.

Adult↗

PubMed1989

A prospective evaluation of a triple-drug regimen containing cisplatin, vinblastine, and dacarbazine (CVD) for metastatic melanoma.

Based on the independent activity of cisplatin, vinblastine, and dimethyl-triazeno-imidazole-carboxamide (DTIC) (CVD), a combination of these agents was used in the treatment of patients with advanced melanoma. Vinblastine was used in a dose of 1.6 mg/m2/d for 5 days, DTIC was used in a dose of 800 mg/m2 intravenously (IV) on day 1, and cisplatin was used in a dose of 20 mg/m2/d for 4 days starting on day 2 of chemotherapy. The courses of chemotherapy were repeated at 3-week intervals. All patients were premedicated with antiemetics, and IV hydration was used before cisplatin. Fifty-two consecutive patients were registered and 50 were evaluable for response. Two patients achieved a complete response (CR) and 18 patients had a partial response (PR) for an overall response rate of 40% (95% confidence interval, 27% to 55%). The median duration of response was 9 months and the median survival time of the responders was 12 months. The overall median survival time of patients treated on this protocol was 9 months. The treatment was associated with significant toxicity consisting of nausea, vomiting, diarrhea, and partial hair loss. Additionally, neutropenia with a median nadir granulocyte count of 500/microliters was observed, and significant anemia required blood transfusions in a majority of the patients after three to four courses of chemotherapy. The dose-limiting toxicity was peripheral neuropathy which required discontinuation of cisplatin after six to eight courses of chemotherapy. We believe that this triple-drug regimen has significant activity that appears to be superior to the single-agent activity of these drugs, both in terms of increased response rate and duration of response.

Adult↗

PubMed1989

Recovery of sperm production after chemotherapy for osteosarcoma.

Because treatment with surgery and combination chemotherapy produces a high cure rate in young men with osteosarcoma, their subsequent reproductive function is an important concern. Semen analyses of osteosarcoma patients, therefore, were performed before, during, and after treatment with the PADIC regimen consisting of cisplatin, Adriamycin (doxorubicin), and dacarbazine or, in some cases, the PADIC regimen plus additional drugs. Results showed that semen volume was not affected and that sperm motility was reduced only during treatment. Although nearly all patients were rendered azoospermic during treatment, sperm production resumed in 30 of 32 patients examined at least 2 years after treatment. Analysis with correction for censored data indicates that, in 78% of treated men, sperm counts will return to more than 10 million/ml. The percentage of men whose sperm counts recovered to normal was lower for those receiving cisplatin dosages greater than or equal to 600 mg/m2; no trends were observed with Adriamycin and dacarbazine dosages. The inclusion of additional drugs such as methotrexate, bleomycin, dactinomycin, or cyclophosphamide (less than 4 g/m2) did not significantly affect the recovery of spermatogenesis. We conclude that the risk of long-term infertility from treatment with the PADIC regimen is low.

Adolescent↗