Intensive weekly chemotherapy for the treatment of extensive-stage small-cell lung cancer.

The regimen of cisplatin, vincristine, doxorubicin, and etoposide (CODE) was designed to double the dose intensity of these drugs in comparison with a standard regimen (alternating cyclophosphamide, doxorubicin, and vincristine [CAV] and etoposide-cisplatin [EP]) for extensive-stage small-cell lung cancer (SCLC). The dose intensity was increased by more frequent treatments rather than by increasing the dose size. The structure of this outpatient protocol includes weekly administration of chemotherapy, alternation of myelosuppressive and nonmyelosuppressive treatments, supportive corticosteroids, gastroprotective agents, and prophylactic antibiotics. Although the duration of chemotherapy was brief (9 to 12 weeks), the total cumulative doses of drugs delivered were similar to the standard regimen. Patients with no residual disease outside the chest after chemotherapy received thoracic irradiation, and patients with complete responses (CRs) received prophylactic cranial irradiation. Eligible extensive-stage SCLC patients were ambulatory, younger than 66 years of age, and free of brain metastasis. Forty-eight extensive-stage SCLC patients were treated. Forty-five (94%) responded to chemotherapy, with 19 (40%) attaining CR. After consolidative thoracic irradiation, the CR rate was 56%. The median time to progression was 43 weeks, and the median survival was 61 weeks. The 2-year survival rate was 30%. The most common site of first relapse was brain (38%). Although two patients (4%) died of toxicity, overall toxicity was acceptable for an outpatient regimen. We conclude that the CODE regimen reliably produces palliative remissions for selected extensive-stage SCLC patients, and it may be associated with durable remissions for some patients. The results of this pilot study are sufficiently promising to justify a phase III trial of CODE versus standard (alternating CAV and EP) chemotherapy.

Abbreviated treatment for elderly, infirm, or noncompliant patients with limited-stage small-cell lung cancer.

PURPOSE: To evaluate the efficacy of an abbreviated treatment plan consisting of two cycles of chemotherapy plus thoracic irradiation in a population of limited-stage small-cell lung cancer (LSCLC) patients who were elderly, infirm, or noncompliant with standard-duration therapy. PATIENTS AND METHODS: Fifty-five LSCLC patients (median age, 73) were treated with one cycle of cyclophosphamide, doxorubicin, and vincristine (CAV) followed 3 weeks later by one cycle of etoposide and cisplatin (EP). Both regimens were administered at conventional full dose. Thoracic irradiation (20 to 30 Gy) was delivered concurrently with EP. RESULTS: Complete response occurred in 28 patients (51%) and partial response in 21 (38%). The median survival time was 54 weeks; the 2-year survival rate was 28% and the actual 5-year survival rate was 18%. Three patients died of toxicity. CONCLUSION: Elderly, infirm, or noncompliant LSCLC patients who are unable to receive standard-duration chemotherapy may have useful palliation and potential for long-term survival with abbreviated chemotherapy (two cycles) and thoracic irradiation.

New combination of the old drugs for elderly patients with small-cell lung cancer: a phase II study of the PAVE regimen.

PURPOSE: A regimen of cisplatin, doxorubicin, vincristine, and etoposide (PAVE) was designed for patients with small-cell lung cancer (SCLC) who were older than 65 years, with the following objectives compared with standard chemotherapy regimens: maintain efficacy, diminish toxicity, enhance compliance, and improve chemotherapy administration convenience at an acceptable cost. PATIENTS AND METHODS: The PAVE regimen consisted of cisplatin 30 mg/m2 intravenously (i.v.) day 1; doxorubicin 40 mg/m2 i.v. day 1; vincristine 1.0 mg/m2 i.v. day 1; and etoposide 100 mg/m2 i.v. day 1 and orally days 3 and 5. Cycles were repeated every 3 weeks for four cycles. Patients with limited-stage disease and selected patients with extensive-stage disease received thoracic irradiation delivered concurrently with etoposide-cisplatin (EP) at the time of the second chemotherapy cycle. RESULTS: Sixty-six eligible patients were treated, which included 25 patients with limited-stage disease and 41 patients with extensive-stage disease. Median survival was 70 weeks and 5-year survival was 25% for limited-stage disease. Median survival was 46 weeks for extensive-stage disease. Only one treatment-related death occurred and severe toxicity was infrequent. The median delivered dose-intensity was according to protocol and the mean delivered total dose was 80% of intended. CONCLUSION: The treatment outcome achieved with PAVE in a phase II study of elderly patients compared favorably with published results of standard regimens in patient populations with better prognostic factors. Because the PAVE regimen can be delivered with good compliance, has acceptable toxicity, and is associated with logistic advantages compared with standard regimens, this protocol is suitable for further investigative trials in elderly patients with SCLC.

Randomized study of CODE versus alternating CAV/EP for extensive-stage small-cell lung cancer: an Intergroup Study of the National Cancer Institute of Canada Clinical Trials Group and the Southwest Oncology Group.

PURPOSE: To determine whether an intensive weekly chemotherapy regimen plus thoracic irradiation is superior to standard chemotherapy in the treatment of extensive-stage small-cell lung cancer (ESCLC). PATIENTS AND METHODS: Patients with ESCLC were considered eligible for the study if they were younger than 68 years, had a performance status of 0 to 2, and were free of brain metastases. Patients were randomized to receive cisplatin, vincristine, doxorubicin, and etoposide (CODE) or alternating cyclophosphamide, doxorubicin, vincristine/etoposide and cisplatin (CAV/EP). Consolidative thoracic irradiation and prophylactic cranial irradiation were given to patients responding to CODE and according to investigator discretion on the CAV/EP arm. RESULTS: The fidelity of drug delivery on both drug regimens was equal, and more than 70% of all patients received the intended protocol chemotherapy. Although rates of neutropenic fever were similar, nine (8.2%) of 110 patients on the CODE arm died during chemotherapy, whereas one (0.9%) of 109 patients died on the CAV/EP arm. Response rates after chemotherapy were higher (P =.006) with CODE (87%) than with CAV/EP (70%). However, progression-free survival (median of 0.66 years on both arms) and overall survival (median, 0.98 years for CODE and 0. 91 years for CAV/EP) were not statistically different. CONCLUSION: The CODE regimen increased two-fold the received dose-intensity of four of the most active drugs in small-cell lung cancer compared with the standard CAV/EP regimen while maintaining an approximately equal total dose. Despite supportive care (but not routine prophylactic use of granulocyte colony-stimulating factor), there was excessive toxic mortality with the CODE regimen. The response rate with CODE was higher than that of CAV/EP, but progression-free and overall survival were not significantly improved. In view of increased toxicity and similar efficacy, the CODE chemotherapy regimen is not recommended for treatment of ESCLC.

Review of conservative surgery in early breast cancer. British Columbia experience.

Conservation mastectomy in combination with radiotherapy is becoming an accepted treatment for early breast cancer. No absolute guidelines exist as to appropriate patient selection or correct surgical technique, but certain unifying trends can be ascertained from the current literature. The purpose of this study was to review the literature and to identify areas of incongruence between present management of patients in British Columbia and suggestions in the current literature. One hundred patients were reviewed. Twenty-six percent of them did not receive preoperative mammograms, and tumor stage was inappropriate in 9 percent. Thirteen percent had excisional biopsies only. A quarter of the patients had tumor resection through unfavorably placed incisions. Eight percent did not have estrogen receptor determination. Thirty-nine percent of the pathology reports made no comment as to adequacy of resection margins. It is hoped that these areas that, with proper attention, can improve cosmetic results and decrease the incidence of local tumor recurrence.

Short versus long duration infusions of paclitaxel for any adenocarcinoma.

BACKGROUND: Paclitaxel has become a standard drug used in a number of common cancers. At first long infusions were used to reduce the rate of inflow of the drug and as a result reduce the occurrence of hypersensitivity types of allergic reactions. Trials with shorter durations of infusion, and using a cocktail of anti-allergic drugs to prevent hypersensitivity reactions, some randomised, were begun. These were interpreted as showing that effectiveness of treatment was not lessened by a short infusion time. These studies also appeared to show that some important toxicities were less common with short infusions and that they were more convenient for the patient and the hospital. OBJECTIVES: To assess the effect of varying the duration of infusion of paclitaxel on its anti-cancer effectiveness and side-effects. SEARCH STRATEGY: Electronic searches of the Cochrane Gynaecological Cancer CRG, the Cochrane Register of Controlled Trials, MEDLINE, EmBase, CANCERLIT, PDQ, Meta-register (mRCT) and the M.D. Anderson Cancer Centre, GOG were carried out. Information from the manufacturer and authors of reports of studies was also acquired. SELECTION CRITERIA: The review was restricted to randomised controlled trials of single agent paclitaxel or paclitaxel with other drugs, where the only variable was the duration of paclitaxel infusion. The review only included patients with advanced adenocarcinoma. DATA COLLECTION AND ANALYSIS: Data was extracted by two independent reviewers and where there was disagreement this was resolved by discussion. Where possible the data was synthesised in a meta-analysis. MAIN RESULTS: Three hour paclitaxel infusions appear to result in a smaller fall in white blood cell count, less fever, infection and sore mouth than 24 hour infusions. In contrast, 24 hour infusions cause less nerve toxicity. Other side-effects are not dependent on the duration of infusion. Evidence from individual trials suggesting efficacy may be slightly greater with 24 hour infusions is inconclusive. Combination of data from trials of different cancer sites in a meta-analysis must be considered speculative, but the combined data also suggest that 24 hour infusions of paclitaxel may be slightly more effective. REVIEWER'S CONCLUSIONS: This review confirms that, apart from neurological effects, three hour infusion of paclitaxel causes significantly less side effects than 24 hour infusion. Insufficient data exists to state whether varying the duration of infusion has a significant effect on its anti-cancer effectiveness. Further study would be required to establish whether there genuinely is a significant difference in efficacy according to the duration of infusion of paclitaxel.

Short versus long duration infusions of paclitaxel for any adenocarcinoma.

BACKGROUND: Paclitaxel has become a standard drug used in a number of common cancers. At first long infusions were used to reduce the rate of inflow of the drug and as a result reduce the occurrence of hypersensitivity types of allergic reactions. Trials with shorter durations of infusion, and using a cocktail of anti-allergic drugs to prevent hypersensitivity reactions, some randomised, were begun. These were interpreted as showing that effectiveness of treatment was not lessened by a short infusion time. These studies also appeared to show that some important toxicities were less common with short infusions and that they were more convenient for the patient and the hospital. OBJECTIVES: To assess the effect of varying the duration of infusion of paclitaxel on its anti-cancer effectiveness and side-effects. SEARCH STRATEGY: Electronic searches of the Cochrane Gynaecological Cancer CRG, the Cochrane Register of Controlled Trials, MEDLINE, EmBase, CANCERLIT, PDQ, Meta-register (mRCT) and the M.D. Anderson Cancer Centre, GOG were carried out. Information from the manufacturer and authors of reports of studies was also acquired. SELECTION CRITERIA: The review was restricted to randomised controlled trials of single agent paclitaxel or paclitaxel with other drugs, where the only variable was the duration of paclitaxel infusion. The review only included patients with advanced adenocarcinoma. DATA COLLECTION AND ANALYSIS: Data was extracted by two independent reviewers and where there was disagreement this was resolved by discussion. Where possible the data was synthesised in a meta-analysis. MAIN RESULTS: Three hour paclitaxel infusions appear to result in a smaller fall in white blood cell count, less fever, infection and sore mouth than 24 hour infusions. In contrast, 24 hour infusions cause less nerve toxicity. Other side-effects are not dependent on the duration of infusion. Evidence from individual trials suggesting efficacy may be slightly greater with 24 hour infusions is inconclusive. Combination of data from trials of different cancer sites in a meta-analysis must be considered speculative, but the combined data also suggest that 24 hour infusions of paclitaxel may be slightly more effective. REVIEWER'S CONCLUSIONS: This review confirms that, apart from neurological effects, three hour infusion of paclitaxel causes significantly less side effects than 24 hour infusion. Insufficient data exists to state whether varying the duration of infusion has a significant effect on its anti-cancer effectiveness. Further study would be required to establish whether there genuinely is a significant difference in efficacy according to the duration of infusion of paclitaxel.

Collagenase immunolocalization studies of cutaneous secondary melanomas.

Immunoreactive collagenase has been demonstrated in 5/14 specimens of cutaneous secondary melanomas. In contrast, very little enzyme was seen in 10 specimens of normal human skin. All specimens were fixed within minutes of excision. These findings support the hypothesis that collagenase facilitates connective-tissue breakdown which is associated with tumour invasiveness and metastatic spread.

Quantitative studies of splenic erythropoiesis in polycythaemia vera and myelofibrosis.

A quantitative scanning method employing cyclotron-produced 52Fe has been developed to assess splenic erythropoiesis in patients with myeloproliferative disorders. In 12 patients with myelofibrosis splenic uptake of 52Fe was from 5.0% to 48% of the injected dose. Although a single patient with classical polycythaemia vera had a minor uptake of 2.8% of six other patients with this diagnosis showed no concentration of isotope in the splenic area. The fraction of 52Fe in the spleen of four patients with 'transitional' myeloproliferative disorders characterized by a high red cell mass, hypercellular bone marrow and a leucoerythroblastic blood film varied from 5% to 41%. No clear relationship was noted between the degree of splenic erythropoiesis as defined by this technique and the level of haemoglobin, the degree of splenomegaly, the effectiveness of erythropoiesis of traditional 59Fe surface counting. If splenectomy is considered in patients with myelofibrosis splenic 52Fe quantitation will provide more precise data on the contribution of splenic erythropoiesis than 59Fe surface counting alone.

Local excision without radiation for high-grade soft-tissue sarcoma of the extremity and superficial trunk.

Purpose. Limb-sparing surgery combined with radiation treatment has become the accepted treatment for patients with high-grade soft-tissue sarcoma. Adjuvant radiation was not routinely used at this institution for patients with clear margins after surgery.This retrospective review analyses the outcome of this group of patients.Patients and methods. Patients studied were referred from 1984 to 1995, were over 16 years of age, were diagnosed with primary high-grade soft-tissue sarcoma of the extremity or superficial trunk, had clear margins after excision and did not receive radiation as a part of their initial treatment. A total of 46 patients were identified.Results. At 5 years, the local control rate was 87%, disease-specific survival was 75% and overall survival was 68%. Of the 6 local recurrences, 3 were located in the buttock (from a total of 7 patients with primary tumours of the buttock), 3 had a primary size of >/= 10 cm (from a total of 8 primary tumours of that size) and all were deep tumours.Discussion. Our data, and those from other reports, suggest that in carefully selected patients appropriate surgery alone results in acceptable local control and survival, and that the morbidity of radiation can be avoided.