Supportive Care Group Research Articles

Bisphosphonates for the relief of pain secondary to bone metastases.

Bisphosphonates form part of standard therapy for hypercalcemia and the prevention of skeletal events in some cancers. However, the role of bisphosphonates in pain relief for bony metastases remains uncertain. To determine the effectiveness of bisphosphonates for the relief of pain from bone metastases. MEDLINE (1966-1999), EMBASE (1980-1999), CancerLit (1966-1999), the Cochrane library (Issue 1, 2000) and the Oxford Pain Database were searched using the strategy devised by the Cochrane Pain, Palliative and Supportive Care Group with additional terms 'diphosphonate', 'bisphosphonate', 'multiple myeloma' and 'bone neoplasms'. (Last search: January 2000). Randomized trials of bisphosphonates compared with open, blinded, or different doses/types of bisphosphonates in cancer patients were included where pain and/or analgesic consumption were outcome measures. Studies where pain was reported only by observers were excluded. Article eligibility, quality assessment and data extraction were undertaken by both reviewers. The proportions of patients with pain relief at 4, 8 and 12 weeks were assessed. The proportion of patients with analgesic reduction, the mean pain score, mean analgesic consumption, adverse drug reactions, and quality of life data were compared as secondary outcomes. Thirty randomized controlled studies (21 blinded, four open and five active control) with a total of 3682 subjects were included. For each outcome, there were few studies with available data. For the proportion of patients with pain relief (eight studies) pooled data showed benefits for the treatment group, with an NNT at 4 weeks of 11[95% CI 6-36] and at 12 weeks of 7 [95% CI 5-12]. In terms of adverse drug reactions, the NNH was 16 [95% CI 12-27] for discontinuation of therapy. Nausea and vomiting were reported in 24 studies with a non-significant trend for greater risk in the treatment group. One study showed a small improvement in quality of life for the treatment group at 4 weeks. The small number of studies in each subgroup with relevant data limited our ability to explore the most effective bisphosphonates and their relative effectiveness for different primary neoplasms. There is evidence to support the effectiveness of bisphosphonates in providing some pain relief for bone metastases. There is insufficient evidence to recommend bisphosphonates for immediate effect; as first line therapy; to define the most effective bisphosphonates or their relative effectiveness for different primary neoplasms. Bisphosphonates should be considered where analgesics and/or radiotherapy are inadequate for the management of painful bone metastases.

The Cochrane Collaboration Pain, Palliative Care and Supportive Care Collaborative Review Group

The Pain, Palliative and Supportive care group is one of 50 collaborative review groups that make up the Cochrane Collaboration, an international organization with the task of preparing, maintaining and disseminating systematic reviews of the effects of healthcare. Cochrane reviews are published cumulatively four times a year on the Cochrane library (CD-ROM and Web-based), along with other useful material such as a register of some 300,000 randomized controlled trials. The group has identified some 20,000 randomized trials in pain and 1,200 in palliative care. Reviews in progress are also published on the library as protocols. Full peer-review is undertaken for protocols and reviews. The Pain, Palliative and Supportive care group is an informal international team involving some 100 people from some 18 countries. The group has published 26 protocols and 17 full reviews with a further 50 reviews in progress. The task is huge and there is scope for further volunteers to help with the various tasks of writing reviews, peer reviewing and literature searching.

The Cochrane Collaboration Pain, Palliative Care and Supportive Care Collaborative Review Group

The Pain, Palliative and Supportive care group is one of 50 collaborative review groups that make up the Cochrane Collaboration, an international organization with the task of preparing, maintaining and disseminating systematic reviews of the effects of healthcare. Cochrane reviews are published cumulatively four times a year on the Cochrane library (CD-ROM and Web-based), along with other useful material such as a register of some 300,000 randomized controlled trials. The group has identified some 20,000 randomized trials in pain and 1,200 in palliative care. Reviews in progress are also published on the library as protocols. Full peer-review is undertaken for protocols and reviews. The Pain, Palliative and Supportive care group is an informal international team involving some 100 people from some 18 countries. The group has published 26 protocols and 17 full reviews with a further 50 reviews in progress. The task is huge and there is scope for further volunteers to help with the various tasks of writing reviews, peer reviewing and literature searching.

Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer

In phase II studies, irinotecan is active in metastatic colorectal cancer, but the overall benefit has not been assessed in a randomised clinical trial. Patients with proven metastatic colorectal cancer, which had progressed within 6 months of treatment with fluorouracil, were randomly assigned either 300-350 mg/m2 irinotecan every 3 weeks with supportive care or supportive care alone, in a 2:1 ratio. 189 patients were allocated irinotecan and supportive care and 90 supportive care alone. The mean age of the participants was 58.8 years; 181 (65%) were men and 98 (35%) were women. WHO performance status was 0 in 79 (42%) patients, 1 in 77 (41%) patients, and 2 in 32 (17%) patients. Tumour-related symptoms were present in 134 (71%) patients and weight loss of more than 5% was seen in 15 (8%) patients. With a median follow-up of 13 months, the overall survival was significantly better in the irinotecan group (p=0.0001), with 36.2% 1-year survival in the irinotecan group versus 13.8% in the supportive-care group. The survival benefit, adjusted for prognostic factors in a multivariate analysis, remained significant (p=0.001). Survival without performance-status deterioration (p=0.0001), without weight loss of more than 5% (p=0.018), and pain-free survival (p=0.003) were significantly better in the patients given irinotecan. In a quality-of-life analysis, all significant differences, except on diarrhoea score, were in favour of the irinotecan group. Our study shows that despite the side-effects of treatment, patients who have metastatic colorectal cancer, and for whom fluorouracil has failed, have a longer survival, fewer tumour-related symptoms, and a better quality of life when treated with irinotecan than with supportive care alone.

Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer

The extent to which chemotherapy may relieve tumour-related symptoms, improve quality of life and prolong survival in patients with gastric cancer is not known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in these patients. Between January 1991 and February 1995, 61 patients with gastric cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was the ELF-regimen consisting of 5-fluorouracil, leucovorin and etoposide, or, in elderly patients with poor performance, a 5-fluorouracil/leucovorin regimen (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument. More patients in the chemotherapy group (45%, 14/31) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (20%, 6/30, P < 0.05). A similar difference was seen in the treating physician's evaluation of whether the patient was subjectively improved or continued to do well for at least 4 months (17/31, 55% versus 6/30, 20%, P < 0.01). Overall survival was longer in the chemotherapy group (median 8 vs. 5 months) although the difference was not statistically significant (P = 0.12). After corrections for imbalances in pretreatment characteristics, chemotherapy treatment was, however, associated with a survival benefit (P = 0.003). Also, the quality-adjusted survival time and time to disease progression were longer for patients randomized to chemotherapy (median 5 vs. 2 months, P = 0.03). The results show that chemotherapy can add to both quantity and quality of life in advanced gastric cancer. The number of patients who benefit from treatment is, however, still rather limited.

Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer

In certain patients with pancreatic and biliary cancer, chemotherapy may relieve tumour-related symptoms, improve quality of life and possibly prolong survival. The extent of these improvements is not completely known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in patients with pancreatic and biliary cancer. Between January 1991 and February 1995, 90 eligible patients with pancreatic or biliary cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was either sequential 5-fluorouracil/leucovorin combined with etoposide (FELv) or, in elderly and poor performance patients, the same regimen without etoposide (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument. Mean scale scores in the QLQ-C30 improved more often/deteriorated less frequently in the chemotherapy group than in the best supportive care group. More patients in the chemotherapy group (36%, 17/49) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (10%, 4/41, P < 0.01). Overall survival was significantly longer in the chemotherapy group (median 6 vs. 2.5 months, P < 0.01). Also, the quality-adjusted survival time was longer for patients randomized to chemotherapy (median 4 vs. 1 months, P < 0.01). The effects were seen both in pancreatic and biliary cancer. The results show that chemotherapy can add to both quantity and quality of life in advanced pancreatic and biliary cancer. The number of patients who benefit from treatment is, however, still limited; for this reason careful selection before, and close monitoring during, treatment are necessary.

Is there a role for melatonin in the treatment of neoplastic cachexia?

It is known that neoplastic cachexia shows metabolic characteristics different from other common causes of malnutrition, and that it is mainly due to an abnormal secretion of TNF, whose levels are often high in patients with advanced neoplasia. Previous clinical studies have suggested that the pineal hormone melatonin (MLT), which plays an essential role in the neuroendocrine regulation of biological systems, may improve the clinical status of advanced cancer patients and inhibit TNF secretion. To investigate the relationship between MLT, TNF and cancer-related weight loss, 100 untreatable metastatic solid tumour patients entered this study to receive either supportive care alone, or supportive care plus MLT (20 mg/day orally in the evening). Patients were observed for 3 months, and were considered evaluable when they were observed for at least 2 months. There were 86 evaluable patients, the other 14 patients having died from rapid progression of disease. The per cent of weight loss greater than 10% was significantly higher in patients treated by supportive care alone than in those concomitantly treated by MLT, with no difference in food intake (P < 0.01). Mean serum levels of TNF progressively increased in the supportive care group, but to levels that were not significantly different from pretreatment values. In contrast, TNF mean concentrations significantly decreased (P < 0.05) in patients concomitantly treated by MLT. These results suggest that the pineal hormone MLT may be effective in the treatment of the neoplastic cachexia by decreasing TNF blood concentrations.

1112 The survival benefit of maintenance therapy of NSCLC pts responding to initial treatment. A randomised trial

NSCLC pts with inoperable disease responding to initial therapy usually fare better than those receiving only supportive care. The aim of this study was to evaluate the role of maintenance therapy after induction chemotherapy (CT) and radiotherapy (RT). 74 pts with NSCLC, stage III–IV, already treated with 8 courses of CT plus RT of the primary site, entered the study. All pts have shown either PR or stable disease. 36 pts were randomly assigned to receive oral cyclophosphamide (CP) 100 mg/m2/day fur 20 days, repeated every 30 days plus IFN-a-2a 3 MU/m2 sq twice weekly, indefinitely (group A). The remaining pts received only supportive care (group B). Two pts in group A had to discontinue treatment because of side-effects and were evaluated as group B pts. Median survival was greater in group A (510 vs 360 days, p < 0.01) and this was also shown with survival analysis (P = 0.005). Hematological toxicity was higher in group A only for WBCs as were also constitutional symptoms. Results show that maintenance therapy with CP and IFN-a-2a confers a survival benefit to those NSCLC pts who have responded to initial therapy. NSCLC pts with inoperable disease responding to initial therapy usually fare better than those receiving only supportive care. The aim of this study was to evaluate the role of maintenance therapy after induction chemotherapy (CT) and radiotherapy (RT). 74 pts with NSCLC, stage III–IV, already treated with 8 courses of CT plus RT of the primary site, entered the study. All pts have shown either PR or stable disease. 36 pts were randomly assigned to receive oral cyclophosphamide (CP) 100 mg/m2/day fur 20 days, repeated every 30 days plus IFN-a-2a 3 MU/m2 sq twice weekly, indefinitely (group A). The remaining pts received only supportive care (group B). Two pts in group A had to discontinue treatment because of side-effects and were evaluated as group B pts. Median survival was greater in group A (510 vs 360 days, p < 0.01) and this was also shown with survival analysis (P = 0.005). Hematological toxicity was higher in group A only for WBCs as were also constitutional symptoms. Results show that maintenance therapy with CP and IFN-a-2a confers a survival benefit to those NSCLC pts who have responded to initial therapy.

Cost-effectiveness of palliative chemotherapy in advanced gastrointestinal cancer

Chemotherapy may relieve tumor-related symptoms, may improve quality of life and prolong survival in advanced gastrointestinal cancer. The extent of such improvements is unclear despite the extensive use of this treatment modality, and there are no studies concerning the economic cost of any gain achieved in the quantity and quality of life by chemotherapy. Between January 1991 and May 1992, 61 patients with inoperable cancer (18 gastric, 22 pancreatic or biliary, and 21 colorectal) were randomized to either primary chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not achieve palliation. All economic costs for medical care were prospectively recorded, and marginal cost-effectiveness analyses were performed. More patients in the primary chemotherapy group (19/33, 58%) had improved/prolonged high quality of life (QoL-patient, minimum duration 4 months) than in the best supportive care group (8/28, 29%, p < 0.05). Overall survival and quality-adjusted survival were significantly longer in the primary chemotherapy group (median 9 vs. 4 months, p < 0.05), and median 7 vs. 2 months, p < 0.05, respectively). When analysed by cancer site, survival was significantly prolonged in gastric cancer patients (median 10 vs. 4 months, p < 0.02), but not in colorectal (median 12 vs. 6 months, p = 0.1) and pancreatic-biliary cancer patients (median 8 vs. 5 months, p = 0.8). The average cost for all medical care was approximately 50% higher in the primary chemotherapy group, but the average cost per day was the same in the two groups. Hospitalization accounted for most of the costs in both groups. The incremental costs per gained year of life was SEK 166,400 ($21,300), per gained quality-adjusted year of life SEK 157,200 ($20,200), and per QoL-patient SEK 160,300 ($20,600). These costs were lower for gastric and colorectal cancer patients, and much higher for pancreatic-biliary cancer patients. The results of this study suggest that palliative chemotherapy is cost-effective in patients with advanced gastric and colorectal cancer. Knowledge about survival and quality of life benefits is still limited in patients suffering from gastric and pancreatic-biliary cancer.

Is there a role for chemotherapy of non-small cell lung cancer?

This paper reviews the results of individual studies and meta-analyses of chemotherapy of non-small cell lung cancer. The published results from studies of chemotherapy as part of a combined modality therapy which have been carried out in the last decade are conflicting. Some show a statistically superior survival for the group receiving chemotherapy compared with a best supportive care group, while the others show no advantage. The differences, however, are small. Meta-analysis of data from published randomized trials has been used by some authors to assess combination chemotherapy compared to supportive or palliative treatment of patients of non-resectable non-small cell lung cancer. In some of the randomized trials and meta-analyses results, a statistically significant effect on survival parameters following chemotherapy against non-small cell lung cancer is shown. The clinical significance of these observations is questionable and the results from larger ongoing trials must be awaited before chemotherapy is used routinely in the treatment of advanced NSCLC.

Cisplatin-Cyclophosphamide-Mitomycin Combination Chemotherapy With Supportive Care Versus Supportive Care Alone for Treatment of Metastatic Non-Small-Cell Lung Cancer

Patients with TNM stage IV non-small-cell lung cancer have short survival times. Previous controlled studies comparing chemotherapy and supportive care for the treatment of this type of cancer have not given consistent results, have included patients with different disease stages, and have rarely reported drug dose intensity. The present trial was designed to assess the safety and the effect on survival of supportive care alone versus chemotherapy with cisplatin, cyclophosphamide, and mitomycin combined with appropriate supportive care in patients with stage IV non-small-cell lung cancer. Patients (n = 102) with stage IV non-small-cell lung cancer were randomly assigned to one of two treatment regimens. The combined modality group (52 patients) received supportive care along with cisplatin (75 mg/m2), cyclophosphamide (400 mg/m2), and mitomycin (10 mg/m2) given intravenously at 3-week intervals. The supportive care group (50 patients) received supportive care alone. Randomization was stratified on the basis of histology (squamous versus nonsquamous cell carcinoma), performance status (Karnofsky), and weight loss (during the 6 months preceding randomization). The two groups were well matched for age and sex. Survival analysis was performed after the last patient died. The median number of chemotherapy cycles was 3.5 per patient. Mean weekly delivered doses of drugs were as follows: cisplatin, 22.1 mg/m2; cyclophosphamide, 118 mg/m2; and mitomycin, 2.9 mg/m2. Toxic effects due to chemotherapy were generally mild, but peripheral neuropathy and hematologic and renal toxic effects were observed. In the supportive care group, mean survival was 6.1 months (median, 4.0 months); six patients lived at least 12 months and two lived at least 18 months. In the combined modality group, mean survival was 11.3 months (median, 8.5 months); 20 patients lived at least 12 months, 13 lived at least 18 months, and five lived at least 24 months. Difference in survival was statistically significant (P < .0001). Survival was directly related to initial performance status in both groups (P < .01) and was significantly (P < .01) longer for patients with squamous cell carcinoma than for those with nonsquamous cell carcinoma. The combination of supportive care and cisplatin-cyclophosphamide-mitomycin therapy offers a survival advantage over supportive care alone in patients with advanced non-small-cell lung cancer. Metastatic non-small-cell lung cancer, generally considered to be unresponsive or marginally responsive to chemotherapy, can be treated with chemotherapy, with an expectation of prolonging patient survival. Although the results of the present study are encouraging, clinical research should continue to be directed toward developing more effective treatments for this disease.

Intravenous hyperalimentation. Effect on delayed cutaneous hypersensitivity in cancer patients.

Effects of nutritional repletion with intravenous hyperalimentation (IVH) on sequential skin test reactivity were evaluated in 160 malnourished cancer patients undergoing chemotherapy (76 patients), surgery (49 patients), radiation therapy (20 patients) and supportive care (15 patients). In the chemotherapy group, 45 patients had negative reactions initially, and 25 patients (55%) had at least one skin test convert to positive in an average period of 19 days of IVH. In the surgery group, 23 patients (46%) were initially positive and remained positive, 13 patients (24%) converted from negative to positive, and 13 patients (30%) remained negative or converted to negative. Postoperative complications occurred in 25% of positive reactors, compared with 69% (p < 0.01) of negative reactors. In the radiation therapy group, the skin tests of six patients (30%) remained positive, three patients (15%) converted from negative to positive and the skin tests of nine patients (45%) remained negative. In the supportive care group, the skin tests of 73% of the patients either remained positive or converted to positive with IVH within an average period of 11 days of treatment. Nutritional therapy with IVH was associated with restored skin test reactivity in 51% of malnourished cancer patients undergoing oncologic therapy. Radiation therapy was generally immunosuppressive despite adequate nutritional repletion. In surgical patients, positive skin test reactivity correlated directly with a favorable response to operative therapy.