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Biomedical subjects

W Steward

Publications and source records attributed to W Steward.

35 records · Page 2Linked to original sources
PubMed1994

rhGM-CSF ameliorates neutropenia in patients with malignant glioma treated with BCNU.

Nitrosoureas are the drugs most effective in the treatment of patients with intracerebral malignant glioma. Their limiting toxicity is delayed myelosuppression. A prospective, randomised crossover study of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was performed in patients receiving BCNU for relapsed glioblastoma, to investigate whether the resulting haematological toxicity profile could be modified by rhGM-CSF. Adequate data for analysis were obtained in 13 patients. Following BCNU, the nadir neutrophil count was higher in 12 out of 13 patients during the rhGM-CSF-protected cycles compared with the unprotected cycles. The median nadir was also significantly higher (1.79, CI 0.76-3.52, P < 0.005). Five episodes of neutropenia (< 2 x 10(9) l-1) occurred during the unprotected cycles compared with none in the rhGM-CSF-protected cycles (P = 0.076). There was no evidence of any effect on platelets. This result shows that the haematological toxicity profile following therapeutic doses of BCNU can be modified. It suggests that rhGM-CSF and other growth factors should be investigated for clinical efficacy in chemotherapy using nitrosoureas.

Adult↗
PubMed1994

Adjuvant CYVADIC chemotherapy for adult soft tissue sarcoma--reduced local recurrence but no improvement in survival: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

PURPOSE: To evaluate the benefit of adjuvant chemotherapy in adult patients with soft tissue sarcomas. The principal end points were freedom from local recurrence and/or metastases and overall survival. PATIENTS AND METHODS: Between January 1977 and June 1988, 468 patients entered this randomized study and 317 were considered eligible. Following complete surgical resection with or without radiotherapy, outcome in 145 eligible patients receiving cyclophosphamide 500 mg/m2 intravenously (IV) bolus on day 1, vincristine 1.4 mg/m2 IV bolus on day 1, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) 50 mg/m2 IV bolus on day 1, and dacarbazine (DTIC) 400 mg/m2 by 1-hour infusion on days 1 to 3 (CYVADIC) cycles repeated every 28 days for eight courses was compared with that in 172 control patients. RESULTS: With a median follow-up duration of 80 months (range, 39 to 165), actuarial percentage survival figures at 7 years were compared. Relapse-free survival rates were higher for CYVADIC, 56% versus 43% (P = .007), and local recurrence was significantly reduced in the CYVADIC arm at 17% versus 31% (P = .004). In contrast, distant metastases occurred with similar frequency in both arms, 32% for CYVADIC versus 36% for control patients (P = .42), and overall survival rates were not significantly different at 63% versus 56% (P = .64). A reduction in local recurrence was only apparent in the group of head, neck, and trunk sarcomas (P = .002), but not in limb tumors (P = .31). CONCLUSION: Adjuvant chemotherapy with CYVADIC cannot be recommended outside the context of a clinical trial. Experience from this study has been used to plan a trial of neoadjuvant chemotherapy with doxorubicin/ifosfamide, which is currently in progress.

Adolescent↗
PubMed1994

A phase II trial with docetaxel (Taxotere) in second line treatment with chemotherapy for advanced breast cancer. A study of the EORTC Early Clinical Trials Group.

BACKGROUND: Docetaxel, a semisynthetic analog of paclitaxel, made for the needles of the European yew, Taxus baccata, is a potentially important chemotherapeutic agent for the treatment of cancer. PATIENTS AND METHODS: In a phase II study patients with advanced and/or metastatic breast cancer and bidimensionally measurable disease, were treated with docetaxel 100 mg/m2 every 3 weeks as a 1 hour infusion without any premedication. Treatment was evaluated after 2 courses and every 2 subsequent courses. RESULTS: Thirty-nine patients were entered, 32 were eligible. The eligible patients had a median age of 51 years (range 30-73) and a performance status WHO 1 median, (range 0-2). Twenty-eight patients had been treated with surgery, 24 with radiation. Hormonal treatment was previously given in 23, chemotherapy in 32. Of 24 patients treated as second line strategy, 13 achieved a partial remission, 1 a complete remission (overall response rate 58% (95% CI 37%-78%)). Eight patients treated as first line: 2 PR's, 1 CR. The median overall response duration was 38 weeks. The main toxicity consisted of transient grade 4 neutropenia in 149 of 167 evaluable courses (89%). However, the related infection rate was low. Re-treatment at 3 weeks, as scheduled, was nearly always possible. Other toxicities consisted of skin reactions (81%) and nail changes (41%), neurosensory toxicity (59%) and occasionally hypersensitivity reactions (16%). Fluid retention was a toxicity of major concern, observed in 59% of patients. CONCLUSION: Docetaxel is a very active drug against breast cancer. Further studies are required to alleviate the non-hematological toxicities.

Adult↗
PubMed1993

Selection of large and objectively measurable target lesions in EORTC phase II trials: impact on recruitment and response rate. EORTC Soft Tissue and Bone Sarcoma Group (STBSG).

The EORTC has recently issued minimum requirements for target lesions in phase II trials, aiming at a decrease in measurement errors [minimum size, computer tomography (CT) scan or ultrasound for deep lesions]. Their impact on recruitment and response has been retrospectively studied in a trial of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG), investigating high-dose chemotherapy in patients with advanced soft tissue sarcoma, where 46/103 objective responses were seen, including 10 complete responses. For the 20 patients who did not satisfy the criteria, a similar objective response rate and a significantly higher complete response rate were reported. Among 265 target lesions, the same trends were observed when comparing small to large lesions, for different tumour sites. For deep lesions clinically assessed, significantly higher response rates were reported than for those measured by CT scans or ultrasound. The new stricter EORTC criteria improve the reliability of measurements and have been adopted for future phase II trials of the STBSG. This will not result in the selection of potentially poor responders. Less than 20% of the present recruitment will be lost.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Ifosfamide plus doxorubicin in previously untreated patients with advanced soft-tissue sarcoma.

The objective of this phase II trial was to assess the therapeutic activity and toxicity of doxorubicin plus ifosfamide in previously untreated patients with advanced soft-tissue sarcoma. Treatment consisted of an intravenous bolus injection of doxorubicin at a dose of 50 mg/m2 followed by a 24-h infusion of ifosfamide at 5 g/m2 plus mesna, with therapy being repeated every 3 weeks until disease progression or unacceptable toxicity occurred. Of the 203 patients entered, 175 were evaluable for response. The overall response rate was 35% (95% confidence interval, 28%-42%), with 9% of patients achieving complete responses and 26% showing partial responses. The median time to progression was 29 weeks for all evaluable patients and 67, 40, and 28 weeks for complete and partial responders and patients with stable disease, respectively. The median duration of survival was 58 weeks. Myelosuppression was the dose-limiting toxicity, resulting in leukopenia (World Health Organization grades 3 and 4) in 73% of the evaluable patients. Other side effects were rare and usually well manageable.

Adolescent↗
PubMed1992

Infection risk in patients with small cell lung cancer receiving intensive chemotherapy and recombinant human granulocyte-macrophage colony-stimulating factor.

The effect of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was assessed in 17 patients with small cell lung cancer. GM-CSF was initially given alone by subcutaneous injection for 10 days at 50-500 micrograms/m2 per day. There was a significant rise in neutrophils and eosinophils and to a lesser extent in monocytes at all dose levels. During the next phase, patients received chemotherapy (etoposide, ifosfamide and doxorubicin), and GM-CSF was given on alternate cycles, the patients acting as their own controls, so that the amelioration of chemotherapy could be assessed. Despite partial abrogation of the neutropenia associated with chemotherapy (P = 0.04), GM-CSF failed to reduce the frequency of febrile episodes in association with neutropenia, with six episodes occurring on GM-CSF and seven while patients were not receiving GM-CSF after a total of 66 cycles of chemotherapy. After GM-CSF, there was a reduction in polymorph phagocytic ability and chemotaxis in 6/12 and 9/11 patients, respectively. Timed blood counts after GM-CSF administration showed that peak leucocytosis occurred at 8-12 h and fell to two-thirds of this level at 24 h. Toxicity consisting of lethargy, myalgia and bone pain occurred at all dose levels but was manageable. 2 patients had thromboembolism. This study failed to demonstrate a reduction in the infection risk associated with moderately intensive chemotherapy for small cell lung cancer despite the partial abrogation of neutropenia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Interferon-alpha 2b in the treatment of follicular lymphoma: preliminary results of a trial in progress.

Since 1985 the combination of chlorambucil (10 mg daily, initially for six weeks, then alternating fortnights for 12 weeks) and interferon-alpha 2b (Schering-Plough; 2 x 10(6) U/m2 three times weekly by subcutaneous injection for 18 weeks) has been compared in a randomised trial with chlorambucil alone in previously untreated patients with stage III or IV follicular lymphoma. Responding patients have subsequently been randomised to receive maintenance interferon-alpha 2b or no further treatment. Of the 124 treated patients, 108 are evaluable for response with a median follow-up of 30 months. The major toxicity was myelosuppression which was more frequent with chlorambucil and IFN alpha 2b in combination than with chlorambucil alone (P less than 0.01). There was no treatment-related mortality. Actuarial survival at three years is 75% for all patients, regardless of therapy. There was no significant difference in response rate according to initial therapy. For the 60 patients achieving a good response to initial therapy who have entered the second part of the trial, there has been a significant prolongation of remission duration in favour of maintenance IFN-alpha 2b (median not yet reached versus two years for the 'no treatment' arm, P less than 0.015). Fewest relapses have been seen in patients who received IFN-alpha 2b throughout. Accrual to this trial continues; this preliminary analysis indicates that maintenance IFN-alpha 2b may extend remission duration in follicular lymphoma.

Adult↗
PubMed1991

EORTC joint ventures in quality control: treatment-related variables and data acquisition in chemotherapy trials.

In multicentre studies, non-compliance with the protocol may limit the chances of reaching a correct conclusion. A procedure to examine the administration of chemotherapy in multicentre EORTC protocols has been developed. General aspects are covered in a mailed questionnaire on the prescription of drugs with rounding up or down of dosages, local facilities for preparation and the procedure for preparation and administration. More detail is collected during a quality control site visit. Ten centres have been visited and there was significant variation between centres in the organisation of chemotherapy administration. However, more striking differences were noted between the type and quality of hospital files. The lack of systematic recording of sequence, timing and doses of chemotherapy and, in particular, treatment related toxicity, is a major difficulty limiting the effectiveness of quality control. These shortcomings emphasise the need for standardisation of some aspects of case records and a suggested check-list has been drafted.

Antineoplastic Agents↗
PubMed1991

Interferon alfa-2b in addition to chlorambucil in the treatment of follicular lymphoma: preliminary results of a randomized trial in progress.

One hundred and twenty four patients with follicular lymphoma (32 with Stage III and 92 with Stage IV disease) have been randomized to receive chlorambucil alone or chlorambucil plus interferon alfa-2b. Responding patients are then randomized to receive either interferon alfa-2b maintenance therapy for up to 12 months or no further treatment. One hundred and eight patients are evaluable for response, the remainder are still receiving initial therapy. Clinical remission (complete or good partial remission) was achieved in 42/59 (71%) patients receiving chlorambucil alone and in 27/49 (55%) patients receiving the combination (P = NS). Preliminary analysis of remission duration shows a trend in favour of those patients receiving interferon throughout (P = 0.02). There is no significant difference between the groups in terms of survival, at a median follow up of 2.5 years. Interferon-associated toxicity was minor in most patients but led to discontinuation of therapy in six cases. Larger trials with longer follow-up periods are needed to confirm the beneficial role of interferon in the treatment of follicular lymphoma.

Adult↗
PubMed1991

High-dose DTIC in advanced soft-tissue sarcomas in the adult. A phase II study of the E.O.R.T.C. Soft Tissue and Bone Sarcoma Group.

Forty-four of 50 adult patients with advanced soft-tissue sarcoma who had received previous chemotherapy were evaluable for response after treatment with DTIC. The therapeutic schedule consisted of DTIC 1.2 g/m2 infused over 20 minutes, and repeated every 3 weeks. There were 1 complete and 7 partial remissions (objective activity 18%, 95% C.I. 7%-29%), with a median duration of 8 weeks (range 5-19), with the complete remission lasting 1 yr. Hematologic toxicity was dose-limiting; W.H.O. greater than or equal to 3 values were observed for WBC in 36%, and for platelets in 26% of patients. The non-hematologic toxicity included nausea and vomiting (90%), a flu-like syndrome (49%), diarrhea (35%), pain in the infused vein (28%) and hypotensive episodes (4%). Intermittent high-dose DTIC is active in advanced soft-tissue sarcoma and should be considered for inclusion in combination regimens.

Adult↗
PubMed1991

Intensive therapy for small-cell lung cancer using carboplatin alternating with cisplatin, ifosfamide, etoposide, mid-cycle vincristine, and radiotherapy.

Forty patients with small-cell lung cancer (31 patients with limited-stage [LS] disease, and nine patients with extensive-stage [ES] disease but of good performance status) have been treated with an intensive therapy composed of carboplatin alternating with cisplatin, ifosfamide, and etoposide with vincristine on day 14 of each carboplatin cycle. A maximum of six cycles were administered at 3 weekly intervals after the cisplatin combination and 4 weekly after the carboplatin combination. Prophylactic cranial irradiation was given with the first cycle of chemotherapy and thoracic irradiation with the third cycle. The median nadir for neutrophils was 0.47 x 10(9)/L and for platelets, 40 x 10(9)/L. Chemotherapy dosages were not reduced in response to myelosuppression, but treatment was delayed to allow blood count recovery. Sixty-eight percent of patients received all six cycles of chemotherapy, and there were four deaths associated with treatment-related neutropenia. Twenty-eight patients (70%) achieved a complete response (CR) when assessed 1 month after the end of treatment, and a further five patients (12.5%) had a partial response (PR). Median duration of CR was 16 months and of PR, 8 months. Cerebral metastases occurred in 20% of all patients and was the apparent sole site of relapse in 11% of the CR patients. The median survival of the total group was 14 months with an actual 2-year survival of 30% and a minimum follow-up of 28 months.

Adult↗
PubMed1988

Review of the clinical trials activity of the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer.

Despite the low incidence of sarcomas, the Soft Tissue and Bone Sarcoma Group has established itself as one of the more active cooperative groups of the European Organization for Research and Treatment of Cancer. Performing over a 10 yr period three phase III protocols (total entry 750 patients), three randomized phase II studies (464 patients), a pilot combination study (185 patients), and 12 phase II studies (406 patients). The new randomized phase III protocol for advanced soft-tissue sarcoma will provide an interesting test of the validity of the current membership policy, which has not discouraged the participation of enthusiastic new members. For extremity sarcomas, improved surgical techniques have increased the number of patients retaining functional limbs but have maintained excellent rates of local control. However, systemic metastasis remains a significant problem and presents a challenge for future adjuvant studies.

Adult↗
PubMedDate not supplied

Factors affecting remission and survival in patients with advanced Hodgkin's disease treated with MVPP.

One hundred and fourteen patients with clinical or pathological stages IIIB and IV Hodgkin's disease have been treated with MVPP chemotherapy followed by radiotherapy to sites of previously bulky disease. The minimum follow-up is 2 years with a median of 5 years. The overall remission rate was 92 per cent with 74 per cent achieving CR. A discriminant analysis showed that the presence of bulky disease was the only independent factor that predicted a lower chance of CR (66 per cent vs 82 per cent, P = 0.045). The 5-year survival was 70 per cent overall and 85 per cent for CR patients. A Cox multivariate analysis demonstrated that stage III disease, age less than 36 years and female sex were all variables which independently predicted a more favourable prognosis in terms of overall survival. However, a similar analysis for survival of CR patients showed that age less than 36 years and the absence of bulky disease were the only two factors to independently predict a more favourable outcome. Of 14 patients who did not receive the chemotherapy according to protocol 5 have relapsed compared to 7 of 70 who did. A Cox analysis confirmed that this variable was the only one of significant prognostic import in predicting relapse-free survival. Using the Cox analyses we have been able to devise a scoring system which accurately predicts the outcome for these patients. This model may be useful in determining which patients have a worse prognosis following treatment with MVPP thus allowing more intensive therapy to be given to such patients while minimising treatment for those with favourable features.

Adolescent↗