Alan Coates

On the receiving end—patient perception of the side-effects of cancer chemotherapy

We conducted a survey to identify and rank side-effects perceived by 99 patients receiving cancer chemotherapy. Non-physical side-effects constituted 54% of the 15 most severe symptoms, and included the thought of coming for treatment, the length of time taken by treatment and having to have a needle. Major physical side-effects were vomiting, nausea and hair loss. Differences in ranking of severity of side-effects were evident when patient groups were divided by sex, age, marital status and domestic situation, as well as by diagnosis, treatment and response. Evaluation of patient perception of the severity of side-effects is an aid to striking the cost benefit balance when deciding whether to use cancer chemotherapy.

On the receiving end—II. Linear analogue self-assessment (LASA) in evaluation of aspects of the quality of life of cancer patients receiving therapy

Linear analogue self-assessment (LASA) scales were used to measure general well-being and specific factors (mood, pain, nausea and vomiting, appetite, breathlessness, physical activity) in patients receiving therapy for malignant melanoma, small cell bronchogenic carcinoma (SCBC) or ovarian cancer. Among the patients with SCBC and melanoma, high correlations were observed between LASA scores for general well-being, mood and appetite. There was a significant relationship between performance status and LASA scores for general well-being, pain and appetite. Among patients with ovarian cancer, there was a significant association between performance status and LASA scores for general well-being, breathlessness and physical activity. Objective response category was related to change in LASA scores for pain. Changes in LASA scores during treatment reflected increased morbidity during radiotherapy in patients also receiving chemotherapy for SCBC. The LASA technique provides a convenient method for the assessment of quality of life in patients receiving cancer therapy, and potentially allows comparison of patient perception of treatment-related morbidities.

Metastatic adenocarcinoma of unknown primary site: a randomized study of two combination chemotherapy regimens

Of 101 patients with symptomatic adenocarcinoma or undifferentiated carcinoma of unknown primary site, 95 were evaluable for the effects of two randomized chemotherapy regimens. Forty-eight patients received combination doxorubicin and mitomycin C (DM) and 47 received combination cisplatin, vinblastine and bleomycin (PB). Response rates were not significantly different between the two treatment groups, 42% for DM and 32% for PVB, with an overall response rate of 37.1%. Survival differences for DM and PVB treated groups were not significantly different, with 18 weeks and 25 weeks median survivals respectively. Toxicities were unequal for the two treatment groups with increased haematological toxicity for DM and greater gastrointestinal toxicity for PVB. The authors conclude both therapies were of limited efficacy in the treatment of ACUP patients and emphasize that only symptomatic patients should be considered for such therapies.

Evidence that treatment with vaccinia melanoma cell lysates (VMCL) may improve survival of patients with stage II melanoma

SummaryA total of 80 patients with melanoma metastases in regional lymph nodes were treated by i.d. injections with a vaccine prepared from a vaccinia virus-infected allogeneic melanoma cell line; 39 patients have been followed for a 2-year period. Interim results from comparison of the treated group with 151 historical controls treated without the vaccine from September 1978 to December 1981 at the same institution and 56 non-randomized concurrent controls suggest that survival was significantly prolonged in the vaccinated group. At the 2-year period overall survival was 75% in the treated compared to 57% in the historical control group. Subset analysis showed a greater apparent benefit of vaccine therapy among patients who had metastases detected at the time of treatment of the primary melanoma (synchronous metastases), while therapy appeared less effective in patients with metastases detected at some time after treatment of the primary (delayed metastases). In the latter only those with one lymph node appeared to benefit from the treatment whereas in patients with synchronous metastases patients with three or more nodes as well as one node appeared to have improved survival. The survival rates at 2 years for treated patients with synchronous metastases in one, two, three or more lymph nodes was 100%, 83% and 79% respectively compared with that of 82%, 86% and 47% respectively in the equivalent control groups. Survival rates in treated patients with delayed metastases in one, two, three or more lymph nodes was 70%, 70% and 65% compared with 47%, 42% and 35% in the equivalent control groups. Treatment and control groups appeared well matched for a number of known prognostic features, including number and size of involved nodes, sex and thickness of primary tumor. Multivariate analysis indicated the effect of treatment was independent of these factors. Despite the empiricism of this approach the present results suggest that this form of therapy warrants further evaluation in a randomized controlled trial.

Immunological effects of recombinant interferon alfa-2a in patients with disseminated melanoma.

Twenty patients with disseminated melanoma were treated with interferon alfa‐2agiven by intramuscular (IM) injection three times a week in escalating doses from 15 to 50 × 106 U/m2. Of 18 patients considered evaluabletwo had complete remission and in two others the disease was stabilized. Laboratory tests 6 hours after injection of interferon alfa‐2a indicated a marked lymphopenia and a reduction in natural killer (NK) cell activity. Sequential changes (measured before injection of interferon alfa‐2a on days 310and 31) consisted of neutropeniathrombocytopeniaand a slight increase in OKT4 positive T cells compared with OKT8 positive T cells. NK activity against the K562 target cells was increased in most patients during the first week of treatmentreturning to near or below pretreatment levels thereafter. This response contrasted with a delayed increase against melanoma target cells in 10 patients. The latter correlated with an increase in mitogen‐stimulated interleukin‐2 (IL2) productionand may indicate that the cytotoxic activity resulted from lymphokine‐activated killer (LAK) cells. Changes in cortisol levels may explain some effects on the immune systemsuch as depression of IL2 and immunoglobulin production in vitroand the differences noted in clinical responses during the present study compared with those observed with interferon alfa‐2b given by intravenous (IV) injection in 5‐day cycles. These results suggest that interferon alfa‐2a has antitumor activity in certain melanoma patientsin particular those with metastases to pulmonary or subcutaneous sites. Assays of IL2 production and LAK activity may assist in the selection of patients who respond to interferon alfa‐2a and help to optimize treatment regimens.

Patient treatment preference in advanced breast cancer: a randomized cross-over study of doxorubicin and mitozantrone.

Twenty-two patients with advanced breast cancer participated in a randomized cross-over study of one cycle each of doxorubicin followed 3 weeks later by mitozantrone or vice versa. Before further treatment, patients selected which drug they wished to continue. Of 18 patients completing the study, 13 chose to continue mitozantrone, 2 doxorubicin and 3 had no preference (P = 0.007). Patients were told to assume similar efficacy of the two drugs and drug preference was based primarily on side-effects. Patient self-assessment of quality of life and physician assigned toxicity scores both indicated that nausea and vomiting, appetite and alopecia were significantly worse following doxorubicin than after mitozantrone. Except for alopecia, no significant period or carry-over effects were noted although the power of the study to detect such interactions was low. This study design may prove useful in enabling patients to select their preference between two treatments of similar efficacy.

Chemotherapy in metastatic melanoma: phase II studies of amsacrine, mitoxantrone and bisantrene

In a phase II study 20 patients with measurable metastatic melanoma were treated with amsacrine 120 mg/m2 every 3 weeks. No objective responses were observed. In a separate study 29 patients received mitoxantrone 12-14 mg/m2 every 3-4 weeks. One objective partial response was seen. The drug was well tolerated. Seventeen patients were treated with bisantrene 135-200 mg/m2 weekly. No objective responses were observed. Phlebitis was the major non-hematologic toxicity of bisantrene. These agents are not recommended for treatment of malignant melanoma.

Drug resistance in clinical practice: Patterns of treatment failure in patients receiving systemic therapy for advanced breast cancer

Strategies for overcoming the causes of drug resistance should take account of the patterns of treatment failure seen in clinical practice. We have analysed the patterns of disease progression in 267 patients with advanced breast cancer receiving systemic therapy. First disease progression on therapy most commonly occurred in tissues involved by tumour at the commencement of treatment. However in 40% of patients, first documentation of disease progression included a tissue not previously known to contain metastatic disease. In only 3% of patients was this new tissue the central nervous system. This pattern of disease progression was not influenced by treatment type (i.e. endocrine or cytotoxic), tumour response to treatment, oestrogen receptor status, prior adjuvant cytotoxic treatment, or disease free interval. These results question the wisdom of always ceasing existing therapy and substituting new treatment when progressive disease is first documented.