Back to:  List of Articles

Cancer treatment in the outpatient setting
(E.Ulsperger, Vienna)

From the perspective of an oncologist in a general hospital it is important to have standard treatment schedules because there is only limited capacity for clinical trials, said Dr. E. Ulsperger, Head of the outpatient department at Lainz-Hospital, Vienna, a hospital with a large proportion of older patients. Treatment schedules are usually derived from clinical trials from which older patients are excluded. One of the major problems in the general hospital is therefore the lack of information about patients beyond the age of 70 since they are generally excluded from protocols but represent a significant proportion in an ageing population.

Lung Cancer

In the treatment of lung cancer one is facing the problem that only a small proportion of patients is diagnosed in stage I (in Austria 23%) which is associated with a relative good prognosis (5 year survival 70%) compared to stage II (5 year survival 35%) and stage III (5 year survival 5%). Thus the overall 5 year survival rate is rather disappointing (5% for small cell lung cancer, 13% for non small cell lung cancer), said Dr. Ulsperger (figure 1).

A very striking result was found in a comparison of the survival rates between 3 time periods in patients with SCLC which was done by Dr. Kokron at Lainz-Hospital. There was no difference at all between 1965-1970 and 1971-1980 although the treatment regimen in the latter period was regarded to be more effective in terms of response rates. In the period from 1981 to 1993 there was a small advantage compared to former times within the first 18 months after starting treatment. But at the end of the 36 month observation period there was no difference between the 3 groups with a survival rate of about 10%. The standard scheme in SCLC is nowadays the combination of adriamycin (60 mg/m²) + cyclophosphamid (750 mg/m²) + vincristin (1 mg/m²). But when looking at the results mentioned before this has to be seen with a question mark, according to Dr. Ulsperger. In NSCLC there are several trials showing an advantage of combination chemotherapy compared to best supportive care as to median survival time and 1 year survival rate.

New treatment options

Gemcitabine seems to be a very promising drug in patients with lung cancer, as was pointed out by Dr. Ulsperger. There are several studies showing a favorable risk/benefit ratio, and this is confirmed by the department's experience in 111 patients. One third of the patients was chemonaive and two thirds had been pretreated before they were switched to gemcitabine. The majority of the patients (63%) had a histological proven diagnosis of adenocarcinoma, 22% presented with a squamous cell carcinoma and 5% with a large cell carcinoma. A SCLC was found in 4% of the patients, 5% had a mixed carcinoma. Gemcitabine was applied as monotherapy in 78% whereas 22% received a combination therapy (13% cisplatin, 9% vinorelbine). The dosage of gemcitabine in monotherapy was 1.250 mg/m² provided that the patients were chemonaive and not older than 70 years. Pretreated patients in the monotherapy group and patients receiving combination therapy were treated with 1.000 mg/m² gemcitabine.

The results in this inhomogenous population are pretty encouraging, said Dr. Ulsperger. 18 patients (16%) showed an objective response, 3 of which had a complete remission. 32% of the patients presented with a minimal response or stable disease, while a progression of the disease was observed in 35%.

What is also of utmost importance from the clinical point of view is the very favorable safety and tolerability profile of gemcitabine in these patients. An overwhelming majority of the patients had no relevant side effects (i. e. WHO grade 0, table 1). Toxicity according to WHO grade 4 was a very rare event. There was no case of alopecia or leucopenia that met WHO 4 criteria and only 4,5% of the patients had WHO 4-thrombopenia. From the patient's point it is also worthwhile to note that nausea and vomiting, two very irritating side effects, were also rare and mild in nature. Half of the patients did not suffer from nausea/vomiting whereas one fifth presented with WHO grade 1 and another fifth with WHO grade 2. Severe nausea/vomiting was reported in 11 % (10% WHO 3, 1 % WHO 4). Based on his own experience Dr. Ulsperger came to the conclusion that gemcitabine has a considerable response rate, also in heavily pretreated patients. The remission rate is comparable to standard treatment whereas the toxicity of gemcitabine is dramatically reduced. Therefore gemcitabine seems to be a good candidate for routine therapy in patients with lung cancer, according to Dr. Ulsperger.

WHO 3 WHO 4 Hairloss   0,9   0 Nause / vomiting   9,9   0,9 Leucopenia   5,4   0 Thrombopenia   4,5   4,5 Flu-like symptoms   12,6   0,9 Cutaneous symptoms   1,8   2,7 Edema   0,9   1,8 table 1: Side effects (WHO grade 3 and 4) under treatment with gemcitabine in patients (n=111) with lung cancer (outpatient department Dr. Ulsperger)

Breast Cancer

When treating patients with breast cancer Dr. Ulsperger refers to the guidelines of the consensus meeting in St. Gallen (1995) defining the usage of adjuvant treatment depending on the stage of the tumor in pre- and postmenopausal women. In node negative premenopausal women there is usually no adjuvant therapy recommended when the patient is in a low risk status. If premenopausal women are presenting with an intermediate risk they should receive tainoxifen, when the tumor is ER-positive, whereas chemotherapy is the first choice in high risk patients. In postmenopausal women tarnoxifen is regarded as first line therapy in both intermediate and high risk patients provided that the tumor is ERpositive. In node positive patients one should also differentiate between preand postmenopausal women. The therapy of choice in premenopausal women is chemotherapy (+/- tamoxifen) whereas in postmenopausal women it's the other way round, said Dr. Ulsperger. Commonly applied chemotherapy schedules in breast cancer are CMF (cyclophosphamid + methotrexate + 5-FU), FEC (5-FU, epirubicine, cyclophosphamid), EC (epirubicine + cyclophosphamid), MiC (mitoxantron + cyclophosphamid) as well as paclitaxel or docetaxel in combination. Although these schedules are effective in some 30% of the patients, improvements in chemotherapy are needed both in efficacy and tolerability. With respect to a better side effect profile there are some promising data with new drugs like gemcitabine in the palliative setting, according to Dr. Ulsperger.

Pancreatic Cancer

Response rates in pancreatic cancer are rather poor. Therefore one should put a special emphasis on quality of life when choosing the optimal treatment, pain relief being one of the major issues in these patients. The side effect profile of the chemotherapy is also of utmost importance because usually the therapy is applied in a palliative setting. Needless to say that the efficacy of the chemotherapy - not only in terms of response rates but also with regard to a more comprehensive evaluation (called clinical benefit) - plays an important role in the selection of the appropriate drug. New hope for improvement has arisen from a comparative trial between gemcitabine and 5-FU showing superiority of gemcitabine in survival rate (18% versus 2% after 12 months, figure 2) and more pronounced clinical benefit.

Bladder Cancer

Pharmacological treatment options in bladder cancer encompass local strategies (mitomycin C, epirubicin, adriamycin, BCG) and systemic application of chemotherapy. One of the most widely used systemic chemotherapy schemes is the M-VAC scheme consisting of methotrexate (30 Mg/M2 : day 1, 15, 22), vinblastin (3 mg/m²: day 2, 15, 22), adriamycin (30 mg/m² : day 2) and cisplatin (70mg/m²: day 2). Although the M-VAC shows considerable response rates there are problems with regard to safety, especially as to kidney function. Therefore, in the treatment of bladder cancer there is a great need for drugs with an improved safety profile. According to Dr. Ulsperger candidates meeting these requirements are paclitaxel or gemcitabine which have proven to be effective as monotherapy in advanced urothelial carcinoma, achieving response rates of about 30% and in combination with platin compounds up to 70%.