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Bec2/BCG Vaccination in SCLC Patients

countries (1-34 patients were recruited per center) ran- domly assigned: 258 to the observation arm and 257 to the vaccination arm. This was an intergroup study to which several cooperative groups in Europe (EORTC Lung Cancer Group, Spanish Lung Cancer Group, Groupe Francais de Pneumo-Cancerologie, and Schweizerische Arbeitsgruppe f¨ur Klinische Krebsforschung), Veteran Administration centers in the United States, and centers in Australia and New Zealand participated. In addition, independent cen- ters also participated in this study.

In the initial part of the study, when patients were registered before starting induction therapy, a total of 195 patients were registered, 89 of whom were randomly as- signed after induction therapy. The major reasons for not being randomly assigned were lack of response or death (46%) or PPD-test positivity (21%). After this stage, the protocol was amended, and patients were no longer regis- tered before the start of induction treatment, and eligible patients were directly assigned randomly after completion of induction. A total of six patients were found to be ineli- gible at randomization, with three in each arm: causes were insufficient induction treatment in two, outside the time- frame for randomization in two, splenectomy in one, and progression after induction in one.

Patient characteristics are listed in Table 1. Major pa- tient characteristics were well balanced between the two arms of the study. The majority of patients who were randomly assigned were men, had good performance status, and had a negative PPD test. In both arms, most patients (93%) received platinum-based chemotherapy (50% cisplatin-etoposide in both arms). Chest radiotherapy was mostly administered con- comitantly with chemotherapy; PCI was delivered to 74% of the patients who had a complete response and to 49% of those who attained a partial response.

Adverse Effects

Positive

12

10

Doubtful

11

10

Negative

78

80

Unknown

0

0.4

Observation (n 258)

Vaccination (n 257)

58 33-81

59 35-89

62 38

63 37

7 93

5 95

Abbreviations: KPS, Karnofsky performance status; PPD, purified protein derivative; PCI, prophylactic cranial irradiation.

  • Ineligible.

Table 1. Major Patient Characteristics at Randomization

Variable

Age, years Median Range Sex, % Male Female KPS, % 60-70

  • 80

PPD, %

58 41 1

38 62

50 50 0

Chest radiotherapy, % Concomitant Sequential Other PCI, % No Yes Response to chemotherapy, %

Complete response Partial response No response

58 39 3

38 62

48 51 1

Just over one third of the skin toxicities were grade 3. These were the main adverse effects that resulted in certain pa- tients refusing to continue treatment. Interestingly, the skin toxicity seems to be less impressive than in most BCG trials, in which 90% to 100% of patients have had grade 3 toxic- ity.8-10,15 There were four toxic deaths in the observation arm

In the vaccination arm, a total of 1,104 vaccinations were given, with a median of five vaccinations (mean, four) per patient and 181 patients (70%) having received all five vaccinations. Fewer than four vaccinations were given to 18% of the patients. The reasons for giving fewer than the five prescribed vaccinations were progression in 54%, re- fusal in 28%, and toxicity in 16%. In total, 9.1% of the vaccinations were attenuated, mainly because of a positive PPD test. A total of 137 vaccinations were delayed for a variety of reasons, but only 17 delays were caused by toxic- ity. The main adverse effects caused by vaccination were local skin toxicity, flu-like symptoms, and lethargy. There were no grade 4 toxicities that were vaccination related. Toxicities are reported in Table 2. The typical skin toxicity, essentially related to the injection of BCG, was manifested by the development of induration then ulceration within the first 3 to 4 weeks, followed by slow healing and scarring in the several weeks after completion of the vaccinations.

Fever

35

14

28

11

Arthralgia

20

8

15

6

3

Lethargy

47

18

40

16

9

Myalgia

20

8

17

7

1

Nausea

17

7

12

5

3

Diarrhea

7

3

3

1

Anorexia

19

7

18

7

2

Skin rash

5

2

4

2

Headache

8

3

5

2

2

Sensory

5

2

1

1

2

Shortness of breath

4

2

4

2

2

Infection

1

1

10

4

1 1 1

1

1 4

  • 1

1

Table 2. Most Common Related Adverse Effects in the Vaccination Arm (n 257)

Grade 1 No.

%

46

18

Adverse Effect

Skin (local)

108

42

92 36

Grade 2

No.

%

Grade 3

No.

%

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