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6B.1 Several drug schedules have been used in the last 2 decades for hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal surface malignancies. Usually the scientific pathway expected to be followed before the introduction of a antiblastic drug (alone or in combination) in the routine clinical practice is outlined below:
However, this pathway has not been strictly respected in the local-regional therapy scenario.
As an example, some drugs have been tested in phase II studies without having been adequately tested in phase I trials.
Fortuitously such situations could have resulted in procedures with acceptable morbidity, which accords with the conceptual goal of local-regional therapy of minimal systemic antiblastic side-effects.
However the disadvantage of such a skipping policy is that the drug (alone of combination) could be adopted by local-regional therapist with a ill-defined suboptimal dose, which does not exploit the whole antiblastic potential of the chemotherapy(ies).
Thus, taking into account the state of the art relative to each of the following drug (or combination) for hyperthermic intraperitoneal chemotherapy, we would like to ask you in which phase it should be allocated to be adequately studied: (just one alternative for each drug(s) allowed)
| Drug/Combination |
a) Not eligible for HIPEC |
b) Experimental phase |
c) Phase I |
d) Phase II |
e) Phase III |
f) Routine clinical use |
| Doxorubicin |
9,68 %
12,50 % |
3,23 %
6,25 % |
6,45 %
9,38 % |
16,13 %
12,50 % |
22,58 %
12,50 % |
41,94 %
46,88 % |
| Melphalan |
25,81 %
25,00 % |
12,90 %
21,88 % |
25,81 %
37,50 % |
19,35 %
6,25 % |
9,68 %
0 % |
6,45 %
9,38 % |
| Mitomycin-C |
3,23 %
12,50 % |
3,23 %
3,13 % |
0 %
0 % |
6,45 %
3,13 % |
22,58 %
9,38 % |
64,52 %
71,88 % |
| Cisplatin |
6,45 %
6,25 % |
0 %
6,25 % |
3,23 %
0 % |
16,13 %
6,25 % |
9,68 %
12,50 % |
64,52 %
68,75 % |
| Gemcitabine |
25,81 %
18,75 % |
19,35 %
37,50 % |
19,35 %
31,25 % |
25,81 %
6,25 % |
6,45 %
3,13 % |
3,23 %
3,13 % |
| Mitoxantrone |
12,90 %
28,13 % |
25,81 %
34,38 % |
29,03 %
15,63 % |
16,13 %
12,50 % |
12,90 %
3,13 % |
3,23 %
6,25 % |
| Oxaliplatin |
0 %
9,38 % |
19,35 %
15,63 % |
9,68 %
9,38 % |
19,35 %
18,75 % |
38,71 %
31,25 % |
12,90 %
15,63 % |
| Etoposide |
19,35 %
28,13 % |
22,58 %
34,38 % |
22,58 %
12,50 % |
16,13 %
9,38 % |
12,90 %
6,25 % |
6,45 %
9,38 % |
| Irinotecan |
9,68 %
18,75 % |
19,35 %
21,88 % |
29,03 %
31,25 % |
22,58 %
15,63 % |
16,13 %
9,38 % |
3,23 %
3,13 % |
| Paclitaxel |
16,13 %
31,25 % |
16,13 %
21,88 % |
19,35 %
21,88 % |
19,35 %
9,38 % |
6,45 %
3,13 % |
22,58 %
12,50 % |
| Docetaxel |
12,90 %
18,75 % |
19,35 %
34,38 % |
29,03 %
31,25 % |
12,90 %
3,13 % |
12,90 %
6,25 % |
12,90 %
6,25 % |
| 5-Fuorouracil |
38,71 %
37,50 % |
9,68 %
15,63 % |
6,45 %
12,50 % |
9,68 %
0 % |
9,68 %
0 % |
25,81 %
34,38 % |
| Carboplatin |
6,45 %
15,63 % |
9,68 %
15,63 % |
25,81 %
21,88 % |
16,13 %
15,63 % |
25,81 %
15,63 % |
16,13 %
15,63 % |
| CDDP+TNF alpha |
12,90 %
15,63 % |
32,26 %
37,50 % |
29,03 %
25,00 % |
19,35 %
12,50 % |
3,23 %
6,25 % |
3,23 %
3,13 % |
| CDDP+Dx |
0 %
9,38 % |
16,13 %
12,50 % |
9,68 %
18,75 % |
25,81 %
6,25 % |
19,35 %
21,88 % |
29,03 %
31,25 % |
| CDDP+MMC |
0 %
9,38 % |
12,90 %
15,63 % |
12,90 %
12,50 % |
12,90 %
6,25 % |
22,58 %
21,88 % |
38,71 %
34,38 % |
| Oxaliplatin ip + leucovorin iv + 5-fluorouracil iv |
0 %
3,13 % |
16,13 %
15,63 % |
19,35 %
15,63 % |
22,58 %
25,00 % |
32,26 %
28,13 % |
9,68 %
12,50 % |
| Oxaliplatin + irinotecan |
6,45 %
9,38 % |
19,35 %
12,50 % |
29,03 %
37,50 % |
16,13 %
12,50 % |
25,81 %
18,75 % |
3,23 %
9,38 % |
| Carboplatin+ INF alpha |
12,90 %
18,75 % |
32,26 %
43,75 % |
29,03 %
28,13 % |
19,35 %
6,25 % |
6,45 %
3,13 % |
0 %
0 % |
6B.2 The choice of carrier solution in which the antineoplastic drug is administered can play an important role in the clearance of drugs from peritoneal cavity to plasma. In the circumstance of a high molecular weight drugs with delayed systemic metabolism or excretion, which one of the following alternatives may present more advantages, according to experimental data? (just one alternative allowed)
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Isotonic salt solutions and dextrose solutions;
First round: 35,48 % - Second round: 53,13 % |
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Hypotonic solutions;
First round: 6,45 % - Second round: 0 % |
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Hypertonic solutions;
First round: 9,68 % - Second round: 0 % |
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Isotonic high molecular weight solutions;
First round: 9,68 % - Second round: 6,25 % |
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The use of carrier solutions of varying tonicity requires further investigation.
First round: 38,71 % - Second round: 40,63 % |
6B.3 The optimal range of temperature (°C) levels during the HIPEC is:
(just one alternative allowed)
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40 – 41;
First round: 0 % - Second round: 0 % |
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41 – 43
First round: 35,48 % - Second round: 62,50 % |
|
41.5 - 42.5
First round: 35,48 % - Second round: 21,88 % |
|
42
First round: 0 % - Second round: 0 % |
|
42 – 42.5
First round: 9,68 % - Second round: 0 % |
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42 – 43
First round: 19,35 % - Second round: 15,63 % |
|
42 - 45
First round: 0 % - Second round: 0 % |
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