Intensive weekly chemotherapy for good-prognosis patients with small-cell lung cancer.

A weekly, intensive chemotherapy regimen has been used to treat 70 patients with small-cell lung cancer (SCLC). Forty-five patients had limited disease (LD) and 25 extensive disease (ED) with good prognostic features. The regimen consisted of cisplatin 50 mg/m2 intravenously (IV) day 1 and etoposide 75 mg/m2 IV days 1 and 2, alternating weekly with ifosfamide 2 g/m2 IV day 8 and doxorubicin 25 mg/m2 IV day 8, for a total of 12 weeks. Dose modifications were made according to defined hematologic criteria. Responding patients with limited disease subsequently received mediastinal radiotherapy. Overall response to chemotherapy was 91% with a complete response (CR) rate of 50%. Forty-five patients with limited disease (LD) achieved an overall response rate of 91% with a CR rate of 51%, and 25 patients with extensive disease (ED) achieved an overall response rate of 92% with a CR rate of 48%. Median survival for the whole group was 54 weeks (LD, 58 weeks; ED, 42 weeks). Hematologic toxicity was predictable, without the wide fluctuations in WBC count seen in conventional 3-weekly regimens. In all, one quarter of treatment courses were delayed, most frequently because of leukopenia. Dose reductions were required in 63% of cases. The average delivered dose intensity was calculated and shown to be 73% of projected. Nonhematologic toxicity was mild with nausea and vomiting being the most common. This weekly schedule of chemotherapy has proved to be active and well tolerated and is currently being compared with conventional 3-weekly chemotherapy in a randomized study.

Received dose-intensity: a randomized trial of weekly chemotherapy with and without granulocyte colony-stimulating factor in small-cell lung cancer.

PURPOSE: A prospective randomized trial to determine if granulocyte colony-stimulating factor (G-CSF) could increase the received dose-intensity (RDI) of weekly chemotherapy in patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS: Forty patients with SCLC with good prognostic features (all patients with limited disease [LD], and extensive-disease [ED] patients with Eastern Cooperative Oncology Group [ECOG] 0 or 1 and plasma alkaline phosphatase levels < 1.5 times the upper limit of normal) were randomized to receive weekly chemotherapy with or without G-CSF. G-CSF (5 micrograms/kg) was self-administered subcutaneously on days when chemotherapy was not given. Chemotherapy consisted of cisplatin 50 mg/m2 intravenously (IV) on day 1 and etoposide 75 mg/m2 IV on days 1 and 2 alternating weekly with ifosfamide 2 g/m2 IV (with mesna) and doxorubicin 25 mg/m2 on day 1, for a total of 12 courses. Dose modifications (dose reductions and treatment delays) were made according to defined hematologic criteria. RESULTS: Dose reductions were made at some point during treatment in 12 of 17 patients in the control arm and in 11 of 23 patients in the G-CSF arm (P = .20). The proportion of patients experiencing dose reductions due to leukopenia was significantly higher in the control arm (nine of 17) compared with the G-CSF arm (four of 23, P < .04). Cycle delays due to leukopenia were similar in both arms of the study. The RDI was 82% of projected in the control arm (95% confidence interval [CI], 79% to 84%) and 84% in patients receiving G-CSF (95% CI, 82% to 87%) (P value not significant). CONCLUSION: In this randomized trial, G-CSF significantly decreased dose reductions due to neutropenia. However, administration of G-CSF did not decrease dose reductions or treatment delays to a level that would allow an increase in received dose-intensity. Nonhematologic toxicities such as increased creatinine concentration also prevented an increase in the RDI in the G-CSF arm.

Outcome of epithelial ovarian cancer in women under 40 years of age treated with platinum-based chemotherapy.

We retrospectively investigated the outcome of ovarian cancer in women aged less than 40 years treated in three randomised phase III studies of platinum-based chemotherapy. 624 patients had invasive epithelial ovarian cancer. A Cox proportional hazard model was used to study prognostic variables. 29 women (5%) were under 40 years of age. Stage, histological grade and amount of residual disease were significantly worse in women aged > or = 40 years. Median follow-up was 66.7 months. At 5 years 65% of women below 40 years of age were alive compared with 20% of older women (95% confidence interval (CI) of the difference 27.1-63.0). The progression-free interval was 59% versus 16% (95% CI 24.3-60.8). No patient under 40 years of age relapsed after 18 months. Age > or = 40 years was a poor prognostic variable, particularly for serous tumours, the commonest subtype in younger women (hazard ratio (HR): 3.33). Other prognostic factors were Eastern Cooperative Oncology Group (ECOG) performance status (HR: 1.25), presence of residual disease (HR: 1.43), histological grade (HR: 1.36) and International Federation of Gynaecology and Obstetrics (FIGO) stage (HR: 1.47). These results suggest that there are biological differences in the behaviour of serous carcinoma of the ovary in women of reproductive age compared with older women.

Hemibody irradiation in multiple myeloma.

Eighteen patients with multiple myeloma were treated by hemibody irradiation using large single fractions, usually to a dose of 10 Gy (lower half) and 7.5 Gy (upper half). All except one patient had previously been treated by multiple courses of conventional chemotherapy with melphalan and prednisone, and were considered to be resistant to further chemotherapy. In most cases, local field irradiation had also been given for symptomatic bone pain. Of the 13 patients who had symptoms at the start of hemibody irradiation, 11 improved sufficiently for their analgesia requirement to be reduced. In eight patients, there was a significant fall in circulating immunoglobulin but no patient with Bence-Jones proteinuria had complete resolution of this biochemical abnormality. Although thrombocytopenia and neutropenia were common, only two patients required platelet transfusion and the treatment was in general extremely well tolerated. Survival following hemibody irradiation was similar to the survival reported from the use of "second-line" chemotherapy and we feel that hemibody irradiation is a more acceptable alternative for most patients.

Increasing social and psychological information conveyed to General Practitioners after bad news consultations by use of separate letters from the Lung Cancer Nurse Specialist.

Multidisciplinary teams (MDT) now review all cases of lung cancer. These teams include a Lung Cancer Nurse Specialist (LCNS). These Nurses help support the patient and should facilitate communication and liaise with other services. The LCNS is present when the diagnosis is given to the patient but also usually spends time afterwards with the patient and their family. We postulated that a separate letter from the LCNS to the General Practitioner (GP) after the consultations would convey extra information to the GP. In 58 new lung cancer patients reviewed in the clinic, the LCNS and Physician independently wrote separate letters after the consultation in which the diagnosis of lung cancer was given. The GPs were asked by questionnaire about the usefulness of the letter from the LCNS. This letter was considered by the GP to provide extra information in: (i) 69% concerning the patients reaction to the diagnosis; (ii) 85% concerning who attended the clinic with the patient; (iii) 85% about what referrals were made to community services; (iv) 86% about who the patient was living with; (v) 81% about who the patients carers were; (vi) 81% information on the patients condition; (vii) 70% concerning the information given to patients about benefits. Ninety-seven percent of the GPs found the LCNS letter useful or very useful and 92% of the GPs thought that the information in the letter would be useful or very useful when they next saw the patient. Separate and independent letters from the LCNS after "bad news" consultation in lung cancer provides added useful information for GPs. Ninety-one percent of the GPs wanted the letters from the LCNS to continue.

A phase II study of ifosfamide in advanced and relapsed carcinoma of the cervix.

Forty-one patients with advanced progressing carcinoma of the cervix were treated with ifosfamide 1.5 g/m2 daily in a 30-min infusion for 5 days every 3 weeks. The overall response rate (complete + partial) was 12/39 (31%), or 12/30 (40%) in those who had not received previous chemotherapy. Six patients achieved a complete remission of disease and four of these remain disease-free 24-39 months later. Durable response were seen in patients with disease progressing after radical radiotherapy. Bone marrow suppression was the dose-limiting toxicity and led to dosage modification in 24 patients. Nausea and vomiting was experienced by all patients at some time during therapy and all patients developed alopecia. Mild neurological toxicity occurred in seven patients but severe life-threatening neurotoxicity was not seen with this schedule of administration. Further studies are needed to identify the optimum dose and schedule of ifosfamide and to ascertain its place in combination therapy.

Telemedicine for multidisciplinary lung cancer meetings.

According to recent UK guidelines on the management of lung cancer, all cases should be reviewed prospectively by a lung cancer multidisciplinary team (MDT) and a thoracic surgeon should be readily available to liaise with the MDT. However, there is a shortage of thoracic surgeons in the UK. Over a one-year period, 28 MDT meetings were held at a district general hospital in Southend, at which 62 patients were presented to a tertiary cardiothoracic centre in London, 80 km away, via ISDN videoconferencing at 384 kbit/s. The annual resection rate increased by 30% following the introduction of the telemedicine MDTmeetings, and the mean time from first being seen in the clinic to surgery was reduced from 69 to 54 days.We estimate that the telemedicine meetings saved over three working weeks of thoracic surgical time during the year.

The effect of radiotherapy on blood mononuclear cell numbers and phagocyte migration.

The effect of localised radiotherapy on whole blood mononuclear cell numbers are on phagocyte migration has been studied in order to relate the effects of treatment to site and volume of radiation. Thirty nine patients who were receiving radiotherapy to five different sites were studied sequentially before, during, and after treatment. Lymphopenia developed with the onset of treatment in the four groups treated with radiotherapy to a large volume. The fall in lymphocyte count affected both T cells and non-T cells, was exponential throughout the period of irradiation, and the rate was independent of site of treatment. Monocyte numbers and phagocyte migration was unaffected. T cells were slightly more radiosensitive than non-T cells and recovery of T cell numbers was usually slow. No effect was seen when superficial radiotherapy was given to a small volume of skin.

Radiation-induced lung fibrosis after treatment of small cell carcinoma of the lung with very high-dose cyclophosphamide.

Twenty-five previously untreated patients with small cell carcinoma of the lung were treated with cyclophosphamide 160 to 200 mg/kg (with autologous bone marrow support) followed by radiotherapy (4000 cGy) to the primary site and mediastinum. No other treatment was given until relapse occurred. Nineteen patients were assessable at least 4 months after radiotherapy; of these, 15 (79%) developed radiologic evidence of fibrosis, which was symptomatic in 14 (74%). The time of onset of fibrosis was related to the volume of lung irradiated. A retrospective analysis was made of 20 consecutive patients treated with multiple-drug chemotherapy and an identical radiotherapy regimen as part of a randomized trial. Radiologic and symptomatic fibrosis was one half as frequent (35%) as in the high-dose cyclophosphamide group. Very high-dose cyclophosphamide appears to sensitize the lung to radiotherapy and promotes the production of fibrosis.

Tropisetron alone or in combination with dexamethasone for the prevention and treatment of emesis induced by non-cisplatin chemotherapy: a randomized trial.

This study compared the efficacy and tolerability of tropisetron (Navoban, Novaban) alone or in combination with dexamethasone for the treatment of emesis induced by moderately emetogenic non-cisplatin chemotherapy. In total, 126 patients with cancer, who had never received chemotherapy and who required at least two courses of moderately emetogenic non-cisplatin chemotherapy each lasting for a minimum of 5 days, were recruited into the study. Patients were randomized to receive tropisetron, 5 mg o.d., plus either dexamethasone, 12 mg i.v. on day 1 followed by 4 mg orally b.i.d. on days 2-5, or placebo. Greater control of acute and delayed vomiting and nausea was achieved in patients given the tropisetron-dexamethasone combination than in those who received the tropisetron-placebo treatment. The majority of adverse events were mild and could be attributed to the chemotherapeutic regimen used or to the underlying disease. Patients and investigators both rated tropisetron alone or in combination with dexamethasone as a highly effective and well-tolerated antiemetic treatment. The results of this study show that tropisetron, 5 mg o.d., is an effective, well-tolerated and simple to use antiemetic treatment for patients receiving moderately emetogenic non-cisplatin chemotherapy. The addition of dexamethasone increases the efficacy of tropisetron without significantly decreasing its tolerability.

A randomised trial of low-dose/high-frequency chemotherapy as palliative treatment of poor-prognosis small-cell lung cancer: a Cancer research Campaign trial.

We report the results of a randomised trial in extensive small-cell lung cancer (SCLC) of a novel approach to palliative chemotherapy. A widely used 3 weekly regimen was compared with the same drugs given at half the dose but twice the frequency with the same intended overall dose intensity (DI). A total of 167 patients defined as having extensive SCLC with adverse prognostic features were randomised to receive either a 3 weekly regimen of cisplatin 60 mg m-2 i.v. on day 1 and etoposide 120 mg m-2 i.v. on day 1 and 100 mg b.d. orally on days 2 and 3 alternating with cyclophosphamide 600 mg m-2 i.v., doxorubicin 50 mg m-2 i.v. and vincristine 2 mg i.v. all on day 1 for a maximum of six courses (3 weekly); or treatment with the same drugs but with each course consisting of half the 3 weekly dose given every 10 or 11 days for a maximum of 12 courses. In the 10/11 day regimen overall response rate was 58.9% (95% CI, 47.9-69.2%) with 12.8% complete responses (CR). For the 3 weekly treatment the overall response rate was 44.9% (95% CI, 35.0-55.5%) with 10.1% CR. Median survival was similar in the two arms at 6.4 months (95% CI, 4.9-7.3 months) and 5.8 months (95% CI, 4.0-6.6 months) respectively. Survival at 1 year was 9.9% (95% CI, 5.0-18.5%) and 8.9% (95% CI, 4.6-16.6%). The 95% CI for the difference in survival at 1 year is -7.09% to +9.09%. Haematological toxicity and treatment delays owing to infection were more frequent with the 10/11 day regimen but other toxicities were equal in both arms. Other aspects of quality of life were measured in a small representative cohort of patients using a daily diary card (DDC). There was a trend of improved quality of life on the 10/11 day arm, but there was little difference between the two treatments. The trial shows that a low-dose/high-frequency regimen with the same DI as conventionally scheduled chemotherapy gives similar response rates and survival. This and other modifications of the schedule may offer new approaches to palliative treatment of advanced cancer. However, in this trial there was no significant benefit in toxicity or other aspects of quality of life.